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A model organism (often shortened to model) is a
non-human Non-human (also spelled nonhuman) is any entity displaying some, but not enough, human characteristics to be considered a human. The term has been used in a variety of contexts and may refer to objects that have been developed with human intelligen ...
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Model organisms are widely used to research human
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
when human experimentation would be unfeasible or
unethical Ethics or moral philosophy is a branch of philosophy that "involves systematizing, defending, and recommending concepts of right and wrong behavior".''Internet Encyclopedia of Philosophy'' The field of ethics, along with aesthetics, concerns ma ...
. This strategy is made possible by the common descent of all living organisms, and the conservation of metabolic and
developmental Development of the human body is the process of growth to maturity. The process begins with fertilization, where an egg released from the ovary of a female is penetrated by a sperm cell from a male. The resulting zygote develops through mitosi ...
pathways and
genetic material Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main clas ...
over the course of
evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
. Studying model organisms can be informative, but care must be taken when generalizing from one organism to another. In researching human
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
, model organisms allow for better understanding the disease process without the added risk of harming an actual human. The species chosen will usually meet a determined taxonomic equivalency to humans, so as to react to disease or its treatment in a way that resembles human
physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
as needed. Although biological activity in a model organism does not ensure an effect in humans, many drugs, treatments and cures for human diseases are developed in part with the guidance of animal models. There are three main types of disease models: homologous, isomorphic and predictive. Homologous animals have the same causes, symptoms and treatment options as would humans who have the same disease. Isomorphic animals share the same symptoms and treatments. Predictive models are similar to a particular human disease in only a couple of aspects, but are useful in isolating and making predictions about mechanisms of a set of disease features. There are many model organisms. One of the first model systems for
molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
was the bacterium ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'', a common constituent of the human digestive system. Several of the bacterial viruses ( bacteriophage) that infect '' E. coli'' also have been very useful for the study of gene structure and
gene regulation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wi ...
(e.g. phages
Lambda Lambda (}, ''lám(b)da'') is the 11th letter of the Greek alphabet, representing the voiced alveolar lateral approximant . In the system of Greek numerals, lambda has a value of 30. Lambda is derived from the Phoenician Lamed . Lambda gave ri ...
and T4). However, it is debated whether bacteriophages should be classified as organisms, because they lack metabolism and depend on functions of the host cells for propagation. Model organisms are drawn from all three domains of life, as well as
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
es. Examples include ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'' (''E. coli''), baker's yeast (''
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...
''), the
T4 phage Escherichia virus T4 is a species of bacteriophages that infect ''Escherichia coli'' bacteria. It is a double-stranded DNA virus in the subfamily ''Tevenvirinae'' from the family Myoviridae. T4 is capable of undergoing only a lytic lifecycle ...
virus, the fruit fly ''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
'', the flowering plant '' Arabidopsis thaliana'',
guinea pig The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ...
s (''Cavia porcellus''), and the mouse (''
Mus musculus Mus or MUS may refer to: Abbreviations * MUS, the NATO country code for Mauritius * MUS, the IATA airport code for Minami Torishima Airport * MUS, abbreviation for the Centre for Modern Urban Studies on Campus The Hague, Leiden University, Net ...
'').


History

The use of animals in research dates back to
ancient Greece Ancient Greece ( el, Ἑλλάς, Hellás) was a northeastern Mediterranean Sea, Mediterranean civilization, existing from the Greek Dark Ages of the 12th–9th centuries BC to the end of Classical Antiquity, classical antiquity ( AD 600), th ...
, with
Aristotle Aristotle (; grc-gre, Ἀριστοτέλης ''Aristotélēs'', ; 384–322 BC) was a Greek philosopher and polymath during the Classical period in Ancient Greece. Taught by Plato, he was the founder of the Peripatetic school of ph ...
(384–322 BCE) and
Erasistratus Erasistratus (; grc-gre, Ἐρασίστρατος; c. 304 – c. 250 BC) was a Greek anatomist and royal physician under Seleucus I Nicator of Syria. Along with fellow physician Herophilus, he founded a school of anatomy in Alexandria, where th ...
(304–258 BCE) among the first to perform experiments on living animals. Discoveries in the 18th and 19th centuries included
Antoine Lavoisier Antoine-Laurent de Lavoisier ( , ; ; 26 August 17438 May 1794),
CNRS (
guinea pig The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ...
in a
calorimeter A calorimeter is an object used for calorimetry, or the process of measuring the heat of chemical reactions or physical changes as well as heat capacity. Differential scanning calorimeters, isothermal micro calorimeters, titration calorimete ...
to prove that
respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellul ...
was a form of combustion, and Louis Pasteur's demonstration of the
germ theory of disease The germ theory of disease is the currently accepted scientific theory for many diseases. It states that microorganisms known as pathogens or "germs" can lead to disease. These small organisms, too small to be seen without magnification, invade ...
in the 1880s using anthrax in sheep. Research using animal models has been central to many of the achievements of modern medicine. It has contributed most of the basic knowledge in fields such as human
physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
and
biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
, and has played significant roles in fields such as
neuroscience Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, developme ...
and
infectious disease An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
.Hau and Shapiro 2011: * * For example, the results have included the near-
eradication of polio The word "Eradication" is derived from Latin word "radix" which means "root". It may refer to: *Eradication of infectious diseases (human), the reduction of the global incidence of an infectious disease in humans to zero *Eradication of infectiou ...
and the development of
organ transplantation Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpor ...
, and have benefited both humans and animals. From 1910 to 1927,
Thomas Hunt Morgan Thomas Hunt Morgan (September 25, 1866 – December 4, 1945) was an American evolutionary biologist, geneticist, embryologist, and science author who won the Nobel Prize in Physiology or Medicine in 1933 for discoveries elucidating the role that ...
's work with the fruit fly ''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
'' identified
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
s as the vector of inheritance for genes. ''Drosophila'' became one of the first, and for some time the most widely used, model organisms, and
Eric Kandel Eric Richard Kandel (; born Erich Richard Kandel, November 7, 1929) is an Austrian-born American medical doctor who specialized in psychiatry, a neuroscientist and a professor of biochemistry and biophysics at the College of Physicians and Surge ...
wrote that Morgan's discoveries "helped transform biology into an experimental science." ''D. melanogaster'' remains one of the most widely used eukaryotic model organisms. During the same time period, studies on mouse genetics in the laboratory of
William Ernest Castle William Ernest Castle (October 25, 1867 – June 3, 1962) was an early American geneticist. Early years William Ernest Castle was born on a farm in Ohio and took an early interest in natural history. He graduated in 1889 from Denison University ...
in collaboration with
Abbie Lathrop Abbie E. C. Lathrop (1868 – 1918) was a rodent fancier who bred fancy mice and inbred strains for animal models, particularly for research on development and hereditary properties of cancer. Biography Lathrop was born in 1868 in Illinois to schoo ...
led to generation of the DBA ("dilute, brown and non-agouti") inbred mouse strain and the systematic generation of other inbred strains. The mouse has since been used extensively as a model organism and is associated with many important biological discoveries of the 20th and 21st centuries. In the late 19th century,
Emil von Behring Emil von Behring (; Emil Adolf von Behring), born Emil Adolf Behring (15 March 1854 – 31 March 1917), was a German physiologist who received the 1901 Nobel Prize in Physiology or Medicine, the first one awarded in that field, for his discovery ...
isolated the
diphtheria Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
toxin and demonstrated its effects in guinea pigs. He went on to develop an antitoxin against diphtheria in animals and then in humans, which resulted in the modern methods of immunization and largely ended diphtheria as a threatening disease. The diphtheria antitoxin is famously commemorated in the Iditarod race, which is modeled after the delivery of antitoxin in the
1925 serum run to Nome The 1925 serum run to Nome, also known as the Great Race of Mercy and The Serum Run, was a transport of diphtheria antitoxin by dog sled relay across the U.S. territory of Alaska by 20 mushers and about 150 sled dogs across in days, saving ...
. The success of animal studies in producing the diphtheria antitoxin has also been attributed as a cause for the decline of the early 20th-century opposition to animal research in the United States. Subsequent research in model organisms led to further medical advances, such as
Frederick Banting Sir Frederick Grant Banting (November 14, 1891 – February 21, 1941) was a Canadian medical scientist, physician, painter, and Nobel laureate noted as the co-discoverer of insulin and its therapeutic potential. In 1923, Banting and Joh ...
's research in dogs, which determined that the isolates of pancreatic secretion could be used to treat dogs with
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
. This led to the 1922 discovery of insulin (with John Macleod) and its use in treating diabetes, which had previously meant death.
John Cade John Frederick Joseph Cade AO (18 January 1912 – 16 November 1980) was an Australian psychiatrist who in 1948 discovered the effects of lithium carbonate as a mood stabilizer in the treatment of bipolar disorder, then known as manic depres ...
's research in guinea pigs discovered the anticonvulsant properties of lithium salts, which revolutionized the treatment of
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
, replacing the previous treatments of lobotomy or electroconvulsive therapy. Modern general anaesthetics, such as
halothane Halothane, sold under the brand name Fluothane among others, is a general anaesthetic. It can be used to induce or maintain anaesthesia. One of its benefits is that it does not increase the production of saliva, which can be particularly useful i ...
and related compounds, were also developed through studies on model organisms, and are necessary for modern, complex surgical operations.Raventos J (1956) ''Br J Pharmacol'' 11, 394Whalen FX, Bacon DR & Smith HM (2005) ''Best Pract Res Clin Anaesthesiol'' 19, 323 In the 1940s,
Jonas Salk Jonas Edward Salk (; born Jonas Salk; October 28, 1914June 23, 1995) was an American virologist and medical researcher who developed one of the first successful polio vaccines. He was born in New York City and attended the City College of New ...
used rhesus monkey studies to isolate the most virulent forms of the
polio Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe s ...
virus, which led to his creation of a
polio vaccine Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all chi ...
. The vaccine, which was made publicly available in 1955, reduced the incidence of polio 15-fold in the United States over the following five years.
Albert Sabin Albert Bruce Sabin ( ; August 26, 1906 – March 3, 1993) was a Polish-American medical researcher, best known for developing the oral polio vaccine, which has played a key role in nearly eradicating the disease. In 1969–72, he served as th ...
improved the vaccine by passing the polio virus through animal hosts, including monkeys; the Sabin vaccine was produced for mass consumption in 1963, and had virtually eradicated polio in the United States by 1965. It has been estimated that developing and producing the vaccines required the use of 100,000 rhesus monkeys, with 65 doses of vaccine produced from each monkey. Sabin wrote in 1992, "Without the use of animals and human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans, but also among animals." Other 20th-century medical advances and treatments that relied on research performed in animals include
organ transplant Organ transplantation is a medical procedure in which an organ (anatomy), organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organ ...
techniques,Carrel A (1912) ''Surg. Gynec. Obst.'' 14: p. 246Williamson C (1926) ''J. Urol.'' 16: p. 231Woodruff H & Burg R (1986) in ''Discoveries in Pharmacology'' vol 3, ed Parnham & Bruinvels, Elsevier, AmsterdamMoore F (1964) ''Give and Take: the Development of Tissue Transplantation''. Saunders, New York the heart-lung machine,Gibbon JH (1937) ''Arch. Surg.'' 34, 1105 antibiotics,Fleming A (1929) ''Br J Exp Path'' 10, 226 and the
whooping cough Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by two or t ...
vaccine.Medical Research Council (1956) ''Br. Med. J.'' 2: p. 454 Treatments for animal diseases have also been developed, including for
rabies Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, ...
,''A reference handbook of the medical sciences''. William Wood and Co., 1904, Edited by Albert H. Buck. anthrax,
glanders Glanders is a contagious zoonotic infectious disease that occurs primarily in horses, mules, and donkeys. It can be contracted by other animals, such as dogs, cats, pigs, goats, and humans. It is caused by infection with the bacterium ''Burkhold ...
,
feline immunodeficiency virus Feline immunodeficiency virus (FIV) is a ''Lentivirus'' that affects cats worldwide, with 2.5% to 4.4% of felines being infected. FIV was first isolated in 1986, by Niels C Pedersen and Janet K. Yamamoto at the UC Davis School of Veterinary M ...
(FIV),
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, i ...
, Texas cattle fever,
classical swine fever Classical swine fever (CSF) or hog cholera (also sometimes called pig plague based on the German word ) is a highly contagious disease of swine ( Old World and New World pigs). It has been mentioned as a potential bioweapon. Clinical signs ...
(hog cholera),
heartworm ''Dirofilaria immitis'', also known as heartworm or dog heartworm, is a parasitic roundworm that is a type of filarial worm, a small thread-like worm, that causes dirofilariasis. It is spread from host to host through the bites of mosquitoe ...
, and other
parasitic infections Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson has ...
. Animal experimentation continues to be required for biomedical research,Sources: * * * * and is used with the aim of solving medical problems such as Alzheimer's disease, AIDS, multiple sclerosis, spinal cord injury, many headaches, and other conditions in which there is no useful ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'' model system available.


Selection

Models are those organisms with a wealth of biological data that make them attractive to study as examples for other
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
and/or natural phenomena that are more difficult to study directly. Continual research on these organisms focuses on a wide variety of experimental techniques and goals from many different levels of biology—from
ecology Ecology () is the study of the relationships between living organisms, including humans, and their physical environment. Ecology considers organisms at the individual, population, community, ecosystem, and biosphere level. Ecology overl ...
, behavior and
biomechanics Biomechanics is the study of the structure, function and motion of the mechanical aspects of biological systems, at any level from whole organisms to organs, cells and cell organelles, using the methods of mechanics. Biomechanics is a branch of ...
, down to the tiny functional scale of individual tissues, organelles and
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s. Inquiries about the DNA of organisms are classed as genetic models (with short generation times, such as the fruitfly and nematode worm),
experimental An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a ...
models, and genomic parsimony models, investigating pivotal position in the evolutionary tree. Historically, model organisms include a handful of species with extensive genomic research data, such as the NIH model organisms. Often, model organisms are chosen on the basis that they are amenable to experimental manipulation. This usually will include characteristics such as short life-cycle, techniques for genetic manipulation (
inbred Inbreeding is the production of offspring from the mating or breeding of individuals or organisms that are closely related genetically. By analogy, the term is used in human reproduction, but more commonly refers to the genetic disorders and o ...
strains, stem cell lines, and methods of
transformation Transformation may refer to: Science and mathematics In biology and medicine * Metamorphosis, the biological process of changing physical form after birth or hatching * Malignant transformation, the process of cells becoming cancerous * Tran ...
) and non-specialist living requirements. Sometimes, the genome arrangement facilitates the sequencing of the model organism's genome, for example, by being very compact or having a low proportion of
junk DNA Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regula ...
(e.g.
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...
, arabidopsis, or pufferfish). When researchers look for an organism to use in their studies, they look for several traits. Among these are size,
generation time In population biology and demography, generation time is the average time between two consecutive generations in the lineages of a population. In human populations, generation time typically ranges from 22 to 33 years. Historians sometimes use this ...
, accessibility, manipulation, genetics, conservation of mechanisms, and potential economic benefit. As comparative
molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
has become more common, some researchers have sought model organisms from a wider assortment of lineages on the
tree of life The tree of life is a fundamental archetype in many of the world's mythological, religious, and philosophical traditions. It is closely related to the concept of the sacred tree.Giovino, Mariana (2007). ''The Assyrian Sacred Tree: A Hist ...
.


Phylogeny and genetic relatedness

The primary reason for the use of model organisms in research is the evolutionary principle that all organisms share some degree of relatedness and genetic similarity due to
common ancestry Common descent is a concept in evolutionary biology applicable when one species is the ancestor of two or more species later in time. All living beings are in fact descendants of a unique ancestor commonly referred to as the last universal com ...
. The study of taxonomic human relatives, then, can provide a great deal of information about mechanism and disease within the human body that can be useful in medicine. Various phylogenetic trees for vertebrates have been constructed using comparative proteomics, genetics, genomics as well as the geochemical and fossil record. These estimations tell us that humans and chimpanzees last shared a common ancestor about 6 million years ago (mya). As our closest relatives, chimpanzees have a lot of potential to tell us about mechanisms of disease (and what genes may be responsible for human intelligence). However, chimpanzees are rarely used in research and are protected from highly invasive procedures. Rodents are the most common animal models. Phylogenetic trees estimate that humans and rodents last shared a common ancestor ~80-100mya. Despite this distant split, humans and rodents have far more similarities than they do differences. This is due to the relative stability of large portions of the genome, making the use of vertebrate animals particularly productive. Genomic data is used to make close comparisons between species and determine relatedness. Humans share about 99% of their genome with chimpanzees (98.7% with bonobos) and over 90% with the mouse. With so much of the genome conserved across species, it is relatively impressive that the differences between humans and mice can be accounted for in approximately six thousand genes (of ~30,000 total). Scientists have been able to take advantage of these similarities in generating experimental and predictive models of human disease.


Use

There are many model organisms. One of the first model systems for
molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
was the bacterium ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'', a common constituent of the human digestive system. Several of the bacterial viruses ( bacteriophage) that infect '' E. coli'' also have been very useful for the study of gene structure and
gene regulation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wi ...
(e.g. phages
Lambda Lambda (}, ''lám(b)da'') is the 11th letter of the Greek alphabet, representing the voiced alveolar lateral approximant . In the system of Greek numerals, lambda has a value of 30. Lambda is derived from the Phoenician Lamed . Lambda gave ri ...
and T4). However, it is debated whether bacteriophages should be classified as organisms, because they lack metabolism and depend on functions of the host cells for propagation. In eukaryotes, several yeasts, particularly ''
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...
'' ("baker's" or "budding" yeast), have been widely used in
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
and cell biology, largely because they are quick and easy to grow. The
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and sub ...
in a simple
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...
is very similar to the cell cycle in
human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...
s and is regulated by homologous proteins. The fruit fly ''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
'' is studied, again, because it is easy to grow for an animal, has various visible congenital traits and has a polytene (giant) chromosome in its salivary glands that can be examined under a light microscope. The
roundworm The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a bro ...
'' Caenorhabditis elegans'' is studied because it has very defined development patterns involving fixed numbers of cells, and it can be rapidly assayed for abnormalities.


Disease models

Animal models serving in research may have an existing, inbred or induced
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
or injury that is similar to a human condition. These test conditions are often termed as animal models of disease. The use of animal models allows researchers to investigate disease states in ways which would be inaccessible in a human patient, performing procedures on the non-human animal that imply a level of harm that would not be considered ethical to inflict on a human. The best models of disease are similar in etiology (mechanism of cause) and phenotype (signs and symptoms) to the human equivalent. However complex human diseases can often be better understood in a simplified system in which individual parts of the disease process are isolated and examined. For instance, behavioral analogues of
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
or pain in laboratory animals can be used to screen and test new drugs for the treatment of these conditions in humans. A 2000 study found that animal models concorded (coincided on true positives and false negatives) with human toxicity in 71% of cases, with 63% for nonrodents alone and 43% for rodents alone. In 1987, Davidson et al. suggested that selection of an animal model for research be based on nine considerations. These include Animal models can be classified as homologous, isomorphic or predictive. Animal models can also be more broadly classified into four categories: 1) experimental, 2) spontaneous, 3) negative, 4) orphan. Experimental models are most common. These refer to models of disease that resemble human conditions in phenotype or response to treatment but are induced artificially in the laboratory. Some examples include: * The use of
metrazol Pentylenetetrazol, also known as pentylenetetrazole, leptazol, metrazol, pentetrazol (INN), pentamethylenetetrazol, Corazol, Cardiazol, Deumacard, or PTZ, is a drug formerly used as a circulatory and respiratory stimulant. High doses cause convul ...
(pentylenetetrazol) as an animal model of
epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...
* Induction of mechanical brain injury as an animal model of
post-traumatic epilepsy Post-traumatic epilepsy (PTE) is a form of acquired epilepsy that results from brain damage caused by physical trauma to the brain (traumatic brain injury, abbreviated TBI). A person with PTE experiences repeated post-traumatic seizures (PTS, s ...
* Injection of the neurotoxin 6-hydroxydopamine to dopaminergic parts of the basal ganglia as an animal model of
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. *
Immunisation Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent (known as the immunogen). When this system is exposed to molecules that are foreign to the body, called ''non-se ...
with an auto-
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
to induce an
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
to model autoimmune diseases such as
Experimental autoimmune encephalomyelitis Experimental autoimmune encephalomyelitis, sometimes experimental allergic encephalomyelitis (EAE), is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with r ...
* Occlusion of the
middle cerebral artery The middle cerebral artery (MCA) is one of the three major paired cerebral arteries that supply blood to the cerebrum. The MCA arises from the internal carotid artery and continues into the lateral sulcus where it then branches and projects to ma ...
as an animal model of ischemic stroke * Injection of blood in the
basal ganglia The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an exter ...
of mice as a model for hemorrhagic stroke *
Sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
and septic shock induction by impairing the integrity of barrier tissues, administering live
pathogens In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...
or toxins * Infecting animals with
pathogens In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...
to reproduce human infectious diseases * Injecting animals with
agonists An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agon ...
or
antagonists An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...
of various neurotransmitters to reproduce human
mental disorder A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitt ...
s * Using ionizing radiation to cause
tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
* Using gene transfer to cause
tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
* Implanting animals with
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s to test and develop treatments using ionizing radiation *
Genetically Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar working i ...
selected (such as in
diabetic Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
mice also known as
NOD mice Non-obese diabetic or NOD mice, like biobreeding rats, are used as an animal model for type 1 diabetes. Diabetes develops in NOD mice as a result of insulitis, a leukocytic infiltrate of the pancreatic islets. The onset of diabetes is associated w ...
) * Various animal models for
screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...
of drugs for the treatment of
glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...
* The use of the ovariectomized rat in osteoporosis research * Use of ''
Plasmodium yoelii ''Plasmodium yoelii'' is a parasite of the genus ''Plasmodium'' subgenus '' Vinckeia''. As in all ''Plasmodium'' species, ''P. yoelii'' has both vertebrate and insect hosts. The vertebrate hosts for this parasite are mammals. Taxonomy This spe ...
'' as a model of human malaria Spontaneous models refer to diseases that are analogous to human conditions that occur naturally in the animal being studied. These models are rare, but informative. Negative models essentially refer to control animals, which are useful for validating an experimental result. Orphan models refer to diseases for which there is no human analog and occur exclusively in the species studied. The increase in knowledge of the
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
s of non-human primates and other
mammals Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur o ...
that are genetically close to humans is allowing the production of
genetically engineered Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including t ...
animal tissues, organs and even animal species which express human diseases, providing a more robust model of human diseases in an animal model. Animal models observed in the sciences of
psychology Psychology is the scientific study of mind and behavior. Psychology includes the study of conscious and unconscious phenomena, including feelings and thoughts. It is an academic discipline of immense scope, crossing the boundaries between ...
and
sociology Sociology is a social science that focuses on society, human social behavior, patterns of social relationships, social interaction, and aspects of culture associated with everyday life. It uses various methods of empirical investigation an ...
are often termed animal models of behavior. It is difficult to build an animal model that perfectly reproduces the symptoms of depression in patients. Depression, as other mental disorders, consists of
endophenotype In genetic epidemiology, endophenotype (or intermediate phenotype) is a term used to separate behavioral symptoms into more stable phenotypes with a clear genetic connection. The concept was coined by Bernard John and Kenneth R. Lewis in a 1966 pap ...
s that can be reproduced independently and evaluated in animals. An ideal animal model offers an opportunity to understand molecular, genetic and epigenetic factors that may lead to depression. By using animal models, the underlying molecular alterations and the causal relationship between genetic or environmental alterations and depression can be examined, which would afford a better insight into
pathology Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...
of depression. In addition,
animal models of depression Animal models of depression are research tools used to investigate depression and action of antidepressants as a simulation to investigate the symptomatology and pathophysiology of depressive illness or used to screen novel antidepressants. In ...
are indispensable for identifying novel
therapies A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many different ...
for depression.


Important model organisms

Model organisms are drawn from all three domains of life, as well as
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
es. The most widely studied
prokaryotic A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
model organism is ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'' (''E. coli''), which has been intensively investigated for over 60 years. It is a common,
gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
gut bacterium which can be grown and cultured easily and inexpensively in a laboratory setting. It is the most widely used organism in
molecular genetics Molecular genetics is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the ...
, and is an important species in the fields of
biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...
and microbiology, where it has served as the
host organism In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...
for the majority of work with
recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
. Simple model eukaryotes include baker's yeast (''
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...
'') and fission yeast (''
Schizosaccharomyces pombe ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measur ...
''), both of which share many characters with higher cells, including those of humans. For instance, many
cell division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...
genes that are critical for the development of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
have been discovered in yeast. ''
Chlamydomonas reinhardtii ''Chlamydomonas reinhardtii'' is a single-cell green alga about 10 micrometres in diameter that swims with two flagella. It has a cell wall made of hydroxyproline-rich glycoproteins, a large cup-shaped chloroplast, a large pyrenoid, and an eye ...
'', a unicellular
green alga The green algae (singular: green alga) are a group consisting of the Prasinodermophyta and its unnamed sister which contains the Chlorophyta and Charophyta/Streptophyta. The land plants (Embryophytes) have emerged deep in the Charophyte alga as ...
with well-studied genetics, is used to study
photosynthesis Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored i ...
and
motility Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
. ''C. reinhardtii'' has many known and mapped mutants and expressed sequence tags, and there are advanced methods for genetic transformation and selection of genes. ''
Dictyostelium discoideum ''Dictyostelium discoideum'' is a species of soil-dwelling amoeba belonging to the phylum Amoebozoa, infraphylum Mycetozoa. Commonly referred to as slime mold, ''D. discoideum'' is a eukaryote that transitions from a collection of unicellular ...
'' is used in
molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
and
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
, and is studied as an example of cell communication, differentiation, and
programmed cell death Programmed cell death (PCD; sometimes referred to as cellular suicide) is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers ...
. Among invertebrates, the fruit fly ''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
'' is famous as the subject of genetics experiments by
Thomas Hunt Morgan Thomas Hunt Morgan (September 25, 1866 – December 4, 1945) was an American evolutionary biologist, geneticist, embryologist, and science author who won the Nobel Prize in Physiology or Medicine in 1933 for discoveries elucidating the role that ...
and others. They are easily raised in the lab, with rapid generations, high
fecundity Fecundity is defined in two ways; in human demography, it is the potential for reproduction of a recorded population as opposed to a sole organism, while in population biology, it is considered similar to fertility, the natural capability to pr ...
, few
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
s, and easily induced observable mutations. The nematode '' Caenorhabditis elegans'' is used for understanding the genetic control of development and physiology. It was first proposed as a model for neuronal development by
Sydney Brenner Sydney Brenner (13 January 1927 – 5 April 2019) was a South African biologist. In 2002, he shared the Nobel Prize in Physiology or Medicine with H. Robert Horvitz and Sir John E. Sulston. Brenner made significant contributions to work ...
in 1963, and has been extensively used in many different contexts since then. ''C. elegans'' was the first multicellular organism whose genome was completely sequenced, and as of 2012, the only organism to have its
connectome A connectome () is a comprehensive map of neural connections in the brain, and may be thought of as its "wiring diagram". An organism's nervous system is made up of neurons which communicate through synapses. A connectome is constructed by tr ...
(neuronal "wiring diagram") completed. '' Arabidopsis thaliana'' is currently the most popular model plant. Its small stature and short generation time facilitates rapid genetic studies,About Arabidopsis on The Arabidopsis Information Resource page
( TAIR) and many phenotypic and biochemical mutants have been mapped. ''A. thaliana'' was the first plant to have its
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
sequenced In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which suc ...
. Among
vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () (chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with c ...
s,
guinea pig The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ...
s (''Cavia porcellus'') were used by
Robert Koch Heinrich Hermann Robert Koch ( , ; 11 December 1843 – 27 May 1910) was a German physician and microbiologist. As the discoverer of the specific causative agents of deadly infectious diseases including tuberculosis, cholera (though the bacteri ...
and other early bacteriologists as a host for bacterial infections, becoming a byword for "laboratory animal," but are less commonly used today. The classic model vertebrate is currently the mouse (''
Mus musculus Mus or MUS may refer to: Abbreviations * MUS, the NATO country code for Mauritius * MUS, the IATA airport code for Minami Torishima Airport * MUS, abbreviation for the Centre for Modern Urban Studies on Campus The Hague, Leiden University, Net ...
''). Many inbred strains exist, as well as lines selected for particular traits, often of medical interest, e.g. body size, obesity, muscularity, and voluntary
wheel-running A hamster wheel or running wheel is an exercise device used primarily by hamsters and other rodents, but also by other Cursorial, cursorial animals when given the opportunity. Most of these devices consist of a runged or ridged wheel held on a ...
behavior. The rat (''
Rattus norvegicus ''Rattus'' is a genus of muroid rodents, all typically called rats. However, the term rat can also be applied to rodent species outside of this genus. Species and description The best-known ''Rattus'' species are the black rat (''R. rattus'') ...
'') is particularly useful as a toxicology model, and as a neurological model and source of primary cell cultures, owing to the larger size of organs and suborganellar structures relative to the mouse, while eggs and embryos from ''
Xenopus tropicalis The western clawed frog (''Xenopus tropicalis'') is a species of frog in the family Pipidae, also known as tropical clawed frog. It is the only species in the genus ''Xenopus'' to have a diploid genome. Its genome has been sequenced, making it a ...
'' and ''
Xenopus laevis The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws ...
'' (African clawed frog) are used in developmental biology, cell biology, toxicology, and neuroscience. Likewise, the
zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ca ...
(''Danio rerio'') has a nearly transparent body during early development, which provides unique visual access to the animal's internal anatomy during this time period. Zebrafish are used to study development, toxicology and toxicopathology, specific gene function and roles of signaling pathways. Other important model organisms and some of their uses include:
T4 phage Escherichia virus T4 is a species of bacteriophages that infect ''Escherichia coli'' bacteria. It is a double-stranded DNA virus in the subfamily ''Tevenvirinae'' from the family Myoviridae. T4 is capable of undergoing only a lytic lifecycle ...
(viral infection), ''
Tetrahymena thermophila ''Tetrahymena thermophila'' is a species of Ciliophora in the family Tetrahymenidae. It is a free living protozoa and occurs in fresh water. There is little information on the ecology and natural history of this species, but it is the most wi ...
'' (intracellular processes),
maize Maize ( ; ''Zea mays'' subsp. ''mays'', from es, maíz after tnq, mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. The ...
(
transposon A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Tra ...
s), '' hydras'' ( regeneration and
morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...
),
cat The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...
s (neurophysiology),
chicken The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adu ...
s (development),
dog The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...
s (respiratory and cardiovascular systems), '' Nothobranchius furzeri'' (aging), and non-human primates such as the
rhesus macaque The rhesus macaque (''Macaca mulatta''), colloquially rhesus monkey, is a species of Old World monkey. There are between six and nine recognised subspecies that are split between two groups, the Chinese-derived and the Indian-derived. Generally ...
and chimpanzee (
hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...
,
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
,
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
, cognition, and
vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.
s).


Selected model organisms

The organisms below have become model organisms because they facilitate the study of certain characters or because of their genetic accessibility. For example, ''E. coli'' was one of the first organisms for which genetic techniques such as
transformation Transformation may refer to: Science and mathematics In biology and medicine * Metamorphosis, the biological process of changing physical form after birth or hatching * Malignant transformation, the process of cells becoming cancerous * Tran ...
or
genetic manipulation Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including ...
has been developed. The
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
s of all model species have been
sequenced In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which suc ...
, including their mitochondrial/ chloroplast genomes.
Model organism databases Model organism databases (MODs) are biological databases, or knowledgebases, dedicated to the provision of in-depth biological data for intensively studied model organisms. MODs allow researchers to easily find background information on large set ...
exist to provide researchers with a portal from which to download sequences (DNA, RNA, or protein) or to access functional information on specific genes, for example the sub-cellular localization of the gene product or its physiological role.


Limitations

Many animal models serving as test subjects in biomedical research, such as rats and mice, may be selectively
sedentary Sedentary lifestyle is a lifestyle type, in which one is physically inactive and does little or no physical movement and or exercise. A person living a sedentary lifestyle is often sitting or lying down while engaged in an activity like soci ...
,
obese Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
and glucose intolerant. This may confound their use to model human metabolic processes and diseases as these can be affected by dietary energy intake and exercise. Similarly, there are differences between the immune systems of model organisms and humans that lead to significantly altered responses to stimuli, although the underlying principles of genome function may be the same. The impoverished environments inside standard laboratory cages deny research animals of the mental and physical challenges are necessary for healthy emotional development. Without day-to-day variety, risks and rewards, and complex environments, some have argued that animal models are irrelevant models of human experience. Mice differ from humans in several immune properties: mice are more resistant to some toxins than humans; have a lower total
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
fraction in the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
, a lower
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
enzymatic Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...
capacity, lower activity of the complement system, and a different set of
pentraxins Pentraxins (PTX), also known as pentaxins, are an evolutionary conserved family of proteins characterised by containing a pentraxin protein domain. Proteins of the pentraxin family are involved in acute immunological responses. They are a clas ...
involved in the inflammatory process; and lack genes for important components of the immune system, such as IL-8, IL-37,
TLR10 Toll-like receptor 10 is a protein that in humans is encoded by the ''TLR10'' gene. TLR10 has also been designated as CD290 ( cluster of differentiation 290). TLR10 has not been extensively studied because it is a pseudogene in mice, though all ot ...
, ICAM-3, etc. Laboratory mice reared in specific-pathogen-free (SPF) conditions usually have a rather immature immune system with a deficit of
memory T cells Memory T cells are a subset of T lymphocytes that might have some of the same functions as memory B cells. Their lineage is unclear. Function Antigen-specific memory T cells specific to viruses or other microbial molecules can be found in both ...
. These mice may have limited diversity of the microbiota, which directly affects the immune system and the development of pathological conditions. Moreover, persistent virus infections (for example, herpesviruses) are activated in humans, but not in SPF mice, with septic complications and may change the resistance to bacterial coinfections. “Dirty” mice are possibly better suitable for mimicking human pathologies. In addition, inbred mouse strains are used in the overwhelming majority of studies, while the human population is heterogeneous, pointing to the importance of studies in interstrain hybrid,
outbred Out-crossing or out-breeding is the technique of crossing between different breeds. This is the practice of introducing distantly related genetic material into a breeding line, thereby increasing genetic diversity. Outcrossing can be a usefu ...
, and nonlinear mice.


Unintended bias

Some studies suggests that inadequate published data in animal testing may result in irreproducible research, with missing details about how experiments are done omitted from published papers or differences in testing that may introduce bias. Examples of hidden bias include a 2014 study from
McGill University McGill University (french: link=no, Université McGill) is an English-language public research university located in Montreal, Quebec Montreal ( ; officially Montréal, ) is the second-most populous city in Canada and most populous ...
in
Montreal, Canada Montreal ( ; officially Montréal, ) is the second-most populous city in Canada and most populous city in the Canadian province of Quebec. Founded in 1642 as '' Ville-Marie'', or "City of Mary", it is named after Mount Royal, the triple-pe ...
which suggests that mice handled by men rather than women showed higher stress levels. Another study in 2016 suggested that gut
microbiomes A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably well ...
in mice may have an impact upon scientific research.


Alternatives

Ethical concerns, as well as the cost, maintenance and relative inefficiency of animal research has encouraged development of alternative methods for the study of disease. Cell culture, or ''in vitro'' studies, provide an alternative that preserves the physiology of the living cell, but does not require the sacrifice of an animal for mechanistic studies. Human, inducible pluripotent stem cells can also elucidate new mechanisms for understanding cancer and cell regeneration. Imaging studies (such as MRI or PET scans) enable non-invasive study of human subjects. Recent advances in genetics and genomics can identify disease-associated genes, which can be targeted for therapies. Many biomedical researchers argue that there is no substitute for a living organism when studying complex interactions in disease pathology or treatments.


Ethics

Debate about the ethical use of animals in research dates at least as far back as 1822 when the British Parliament under pressure from British and Indian intellectuals enacted the first law for animal protection preventing cruelty to cattle. This was followed by the Cruelty to Animals Act of 1835 and 1849, which criminalized ill-treating, over-driving, and torturing animals. In 1876, under pressure from the
National Anti-Vivisection Society The National Anti-Vivisection Society (NAVS) is an international not-for-profit animal protection group, based in London, working to end animal testing, and focused on the replacement of animals in research with advanced, scientific techniques. S ...
, the Cruelty to Animals Act was amended to include regulations governing the use of animals in research. This new act stipulated that 1) experiments must be proven absolutely necessary for instruction, or to save or prolong human life; 2) animals must be properly anesthetized; and 3) animals must be killed as soon as the experiment is over. Today, these three principles are central to the laws and guidelines governing the use of animals and research. In the U.S., the Animal Welfare Act of 1970 (see also Laboratory Animal Welfare Act) set standards for animal use and care in research. This law is enforced by APHIS's Animal Care program. In academic settings in which NIH funding is used for animal research, institutions are governed by the NIH Office of Laboratory Animal Welfare (OLAW). At each site, OLAW guidelines and standards are upheld by a local review board called the Institutional Animal Care and Use Committee (IACUC). All laboratory experiments involving living animals are reviewed and approved by this committee. In addition to proving the potential for benefit to human health, minimization of pain and distress, and timely and humane euthanasia, experimenters must justify their protocols based on the principles of Replacement, Reduction and Refinement. "Replacement" refers to efforts to engage alternatives to animal use. This includes the use of computer models, non-living tissues and cells, and replacement of “higher-order” animals (primates and mammals) with “lower” order animals (e.g. cold-blooded animals, invertebrates) wherever possible.list of common model organisms approved for use by the NIH
 "Reduction" refers to efforts to minimize number of animals used during the course of an experiment, as well as prevention of unnecessary replication of previous experiments. To satisfy this requirement, mathematical calculations of statistical power are employed to determine the minimum number of animals that can be used to get a statistically significant experimental result. "Refinement" refers to efforts to make experimental design as painless and efficient as possible in order to minimize the suffering of each animal subject.


See also

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Animals in space Animals in space originally served to test the survivability of spaceflight, before human spaceflights were attempted. Later, other non-human animals were flown to investigate various biological processes and the effects microgravity and space ...
*
Animal testing Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This ...
* Animal testing on invertebrates *
Animal testing on rodents Rodents are commonly used in animal testing, particularly mice and rats, but also guinea pigs, hamsters, gerbils and others. Mice are the most commonly used vertebrate species, due to their availability, size, low cost, ease of handling, and fast ...
* Cellular model (numerical), e.g., ''
Mycoplasma genitalium ''Mycoplasma genitalium'' (''MG'', commonly known as Mgen) is a sexually transmitted, small and pathogenic bacterium that lives on the mucous epithelial cells of the urinary and genital tracts in humans. Medical reports published in 2007 and 2 ...
''. *
Ensembl Ensembl genome database project is a scientific project at the European Bioinformatics Institute, which provides a centralized resource for geneticists, molecular biologists and other researchers studying the genomes of our own species and other v ...
genome database of model organisms *
Generic Model Organism Database The Generic Model Organism Database (GMOD) project provides biological research communities with a toolkit of open-source software components for visualizing, annotating, managing, and storing biological data. The GMOD project is funded by the Unit ...
*
Genome project Genome projects are scientific endeavours that ultimately aim to determine the complete genome sequence of an organism (be it an animal, a plant, a fungus, a bacterium, an archaean, a protist or a virus) and to annotate protein-coding genes and o ...
*
History of animal testing The history of animal testing goes back to the writings of the Ancient Greeks in the 4th and 3rd centuries BCE, with Aristotle (384–322 BCE) and Erasistratus (304–258 BCE) one of the first documented to perform experiments on nonhuman animals. ...
*
History of model organisms The history of model organisms began with the idea that certain organisms can be studied and used to gain knowledge of other organisms or as a control (ideal) for other organisms of the same species. Model organisms offer standards that serve as ...
* History of research on '' Arabidopsis thaliana'' * History of research on '' Caenorhabditis elegans'' *
Mouse models of breast cancer metastasis Breast cancer metastatic mouse models are experimental approaches in which mice are genetically manipulated to develop a mammary tumor leading to distant focal lesions of mammary epithelium created by metastasis. Mammary cancers in mice can be ca ...
*
Mouse models of colorectal and intestinal cancer Mouse models of colorectal cancer and intestinal cancer are experimental systems in which mice are genetically manipulated, fed a modified diet, or challenged with chemicals to develop malignancies in the gastrointestinal tract. These models enab ...
*
RefSeq The Reference Sequence (RefSeq) database is an open access, annotated and curated collection of publicly available nucleotide sequences ( DNA, RNA) and their protein products. RefSeq was first introduced in 2000. This database is built by National ...
- the Reference Sequence database


References


Further reading

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External links

* Wellcome Trust description of model organisms
National Institutes of Health Comparative Medicine Program Vertebrate Models

NIH Using Model Organisms to Study Human Disease

National Institutes of Health Model Organism Sharing Policy



Disease Animal Models – BSRC Alexander Fleming

Emice
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National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

Knock Out Mouse Project – KOMP

Mouse Biology Program

Mutant Mouse Resource & Research Centers, National Institutes of Health, supported Mouse Repository

Rat Resource & Research Center
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National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
, supported Rat Repository
NIH Model Organism Research Reproducibility and Rigor
{{DEFAULTSORT:Model Organism Animal testing