Animal testing on rodents
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Rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...
s are commonly used in
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 ...
, particularly
mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...
and
rats Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' (pack rats), '' Bandicota'' (bandicoot ...
, but also
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,
hamster Hamsters are rodents (order Rodentia) belonging to the subfamily Cricetinae, which contains 19 species classified in seven genera.Fox, Sue. 2006. ''Hamsters''. T.F.H. Publications Inc. They have become established as popular small pets. The ...
s,
gerbil The Mongolian gerbil or Mongolian jird (''Meriones unguiculatus'') is a small rodent belonging to the subfamily Gerbillinae. Their body size is typically , with a tail, and body weight , with adult males larger than females. The animal is us ...
s and others. Mice are the most commonly used vertebrate species, due to their availability, size, low cost, ease of handling, and fast reproduction rate. __TOC__


Statistics

In the UK in 2015, there were 3.33 million procedures on rodents (80% of total procedures that year). The most common species used were mice (3.03 million procedures, or 73% of total) and rats (268,522, or 6.5%). Other rodents species included guinea pigs (21,831 / 0.7%), hamsters (1,500 / 0.04%) and gerbils (278 / 0.01%). In the U.S., the numbers of rats and mice used are not reported, but estimates range from around 11 million to approximately 100 million. In 2000, the Federal Research Division, Library of Congress, published the results of an analysis of its Rats/Mice/and Birds Database: Researchers, Breeders, Transporters, and Exhibitors.


Rodent types


Mice

Mice are the most commonly used vertebrate species, popular because of their availability, size, low cost, ease of handling, and fast reproduction rate. Mice are quick to reach sexual maturity, as well as quick to
gestate Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during preg ...
, where labs can have a new generation every three weeks as well as a relatively short lifespan of two years. They are widely considered to be the prime model of inherited human disease and share 99% of their
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s with humans.The Measure Of Man
Sanger Institute Press Release, 5 December 2002
With the advent of
genetic engineering 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 ...
technology, genetically modified mice can be generated to order and can cost hundreds of dollars each. Transgenic animal production consists of injecting each construct into 300–350 eggs, typically representing three days' work. Twenty to fifty mice will normally be born from this number of injected eggs. These animals are screened for the presence of the
transgene A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change t ...
by a
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
genotyping assay. The number of transgenic animals typically varies from two to eight. Chimeric mouse production consists of injecting
embryonic stem cells Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist ...
provided by the investigator into 150–175 blastocysts, representing three days of work. Thirty to fifty live mice are normally born from this number of injected
blastocyst The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called th ...
s. Normally, the skin color of the mice from which the host blastocysts are derived is different from that of the strain used to produce the embryonic stem cells. Typically two to six mice will have skin and hair with greater than seventy percent ES cell contribution, indicating a good chance for embryonic stem cell contribution to the
germline In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They ...
.


Syrian hamsters

Syrian hamsters The golden hamster or Syrian hamster (''Mesocricetus auratus'') is a rodent belonging to the hamster subfamily, Cricetinae. Their natural geographical range is in an arid region of northern Syria and southern Turkey. Their numbers have been de ...
are used to model the human medical conditions including various cancers, metabolic diseases, non-cancer respiratory diseases, cardiovascular diseases, infectious diseases, and general health concerns. In 2006–07, Syrian hamsters accounted for 19% of the total animal research participants in the United States.


Rats

Rodents such as rats are the most common model in researching effects of cardiovascular disease, as the effects on rodents mimic those in humans. Rats have also been used as tools in research to try to find if there is a difference in the effects of cocaine on adults versus adolescents.


Limitations

While mice, rats and other rodents are by far the most widely used animals in biomedical research, recent studies have highlighted their limitations. For example, the utility of the use of rodents in testing for sepsis, burns, inflammation, stroke, ALS, Alzheimer's, diabetes, cancer, multiple sclerosis, Parkinson's disease and other illnesses has been called into question by a number of researchers. Regarding experiments on mice in particular, some researchers have complained that "years and billions of dollars have been wasted following false leads" as a result of a preoccupation with the use of these animals in studies. Mice differ from humans in several immune properties: mice are more resistant to some
toxins A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849â ...
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 capacity, lower activity of the
complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and ...
, 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. These mice may have limited diversity of the
microbiota Microbiota are the range of microorganisms that may be commensal, symbiotic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found ...
, 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 Coinfection is the simultaneous infection of a host by multiple pathogen species. In virology, coinfection includes simultaneous infection of a single cell by two or more virus particles. An example is the coinfection of liver cells with hepatiti ...
. "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 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, culture, ...
is heterogeneous, pointing to the importance of studies in interstrain hybrid, outbred, and nonlinear mice. An article in '' The Scientist'' notes, "The difficulties associated with using animal models for human disease result from the metabolic, anatomic, and cellular differences between humans and other creatures, but the problems go even deeper than that" including issues with the design and execution of the tests themselves. For example, researchers have found that many rats and mice in laboratories are obese from excess food and minimal exercise which alters their physiology and drug metabolism. Many laboratory animals, including mice and rats, are chronically stressed which can also negatively affect research outcomes and the ability to accurately extrapolate findings to humans. Researchers have also noted that many studies involving mice, rats and other rodents are poorly designed, leading to questionable findings. One explanation for deficiencies in studies of rodents housed in laboratory cages is that they lack access to environmental agency and thus the ongoing freedom to make decisions and experience their consequences. By housing rodents under extreme impoverished conditions, these captive animals bear diminished resemblance to humans or their wild conspecifics. Some studies suggests that inadequate published data in animal testing may result in irreproducible research, with missing details about how experiments are done are 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, Canada. Founded in 1821 by royal charter granted by King George IV,Frost, Stanley Brice. ''McGill Univer ...
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 in mice may have an impact upon scientific research.


See also

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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 model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...
*
BALB/c BALB/c is an albino, laboratory-bred strain of the house mouse from which a number of common substrains are derived. Now over 200 generations from New York in 1920, BALB/c mice are distributed globally, and are among the most widely used inbred ...
*
C57BL/6 C57BL/6, often referred to as "C57 black 6", "C57" or "black 6", is a common inbred strain of laboratory mouse. It is the most widely used "genetic background" for genetically modified mice for use as models of human disease. They are the most wid ...
*
Fe, Fi, Fo, Fum, and Phooey Fe, Fi, Fo, Fum, and Phooey were five mice who traveled to the Moon and circled it 75 times on the 1972 Apollo 17 mission. NASA gave them identification numbers A3305, A3326, A3352, A3356, and A3400, and their nicknames were given by the Apollo 1 ...
, five mice who orbited the Moon in 1972 * Mouse models of colorectal and intestinal cancer *
Preclinical imaging Preclinical imaging is the visualization of living animals for research purposes, such as drug development. Imaging modalities have long been crucial to the researcher in observing changes, either at the organ, tissue, cell, or molecular level, i ...
* Rat Park *
Testing cosmetics on animals Cosmetic testing on animals is a type of animal testing used to test the safety and hypoallergenic properties of cosmetic products for use by humans. Since this type of animal testing is often harmful to the animal subjects, it is opposed by an ...
*
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 c ...


References


Sources

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External links


Information about mouse models
from HOPES: Huntington's Disease Outreach Project for Education at Stanford
Animal Model of Disease
from Animal Research Organization {{Authority control Animal testing on rodents