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The laboratory mouse or lab mouse is a small mammal of the order
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 ...
ia which is bred and used for
scientific research The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific m ...
or feeders for certain pets. Laboratory mice are usually of the species ''
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 ...
''. They are the most commonly used mammalian research model and are used for research 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 ...
,
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 ...
,
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 ...
,
medicine Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pr ...
and other
scientific Science is a systematic endeavor that builds and organizes knowledge in the form of testable explanations and predictions about the universe. Science may be as old as the human species, and some of the earliest archeological evidence for ...
disciplines. Mice belong to the
Euarchontoglires Euarchontoglires (synonymous with Supraprimates) is a clade and a superorder of mammals, the living members of which belong to one of the five following groups: rodents, lagomorphs, treeshrews, colugos, and primates. Evolutionary affinities wi ...
clade, which includes humans. This close relationship, the associated high homology with humans, their ease of maintenance and handling, and their high reproduction rate, make mice particularly suitable models for human-oriented research. The laboratory mouse genome has been sequenced and many mouse genes have human homologues. Other mouse species sometimes used in laboratory research include two American species, the
white-footed mouse The white-footed mouse (''Peromyscus leucopus'') is a rodent native to North America from Ontario, Quebec, Labrador, and the Maritime Provinces (excluding the island of Newfoundland) to the southwestern United States and Mexico. In the Maritimes, ...
(''Peromyscus leucopus'') and the North American deer mouse (''
Peromyscus maniculatus ''Peromyscus maniculatus'' is a rodent native to eastern North America. It is most commonly called the eastern deer mouse; when formerly grouped with the western deer mouse (''P. sonoriensis''), it was referred to as the North American deermou ...
'').


History as a biological model

Mice have been used in biomedical research since the 17th Century (from May 30, 1678) when
William Harvey William Harvey (1 April 1578 – 3 June 1657) was an English physician who made influential contributions in anatomy and physiology. He was the first known physician to describe completely, and in detail, the systemic circulation and propert ...
used them for his studies on reproduction and blood circulation and Robert Hooke used them to investigate the biological consequences of an increase in air pressure. During the 18th century
Joseph Priestley Joseph Priestley (; 24 March 1733 – 6 February 1804) was an English chemist, natural philosopher, separatist theologian, grammarian, multi-subject educator, and liberal political theorist. He published over 150 works, and conducted exp ...
and
Antoine Lavoisier Antoine-Laurent de Lavoisier ( , ; ; 26 August 17438 May 1794),
CNRS (
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 ...
. In the 19th century
Gregor Mendel Gregor Johann Mendel, OSA (; cs, Řehoř Jan Mendel; 20 July 1822 – 6 January 1884) was a biologist, meteorologist, mathematician, Augustinian friar and abbot of St. Thomas' Abbey in Brünn (''Brno''), Margraviate of Moravia. Mendel was ...
carried out his early investigations of inheritance on mouse coat color but was asked by his superior to stop breeding in his cell "smelly creatures that, in addition, copulated and had sex". He then switched his investigations to peas but, as his observations were published in a somewhat obscure botanical journal, they were virtually ignored for over 35 years until they were rediscovered in the early 20th century. In 1902 Lucien Cuénot published the results of his experiments using mice which showed that Mendel's laws of inheritance were also valid for animals — results that were soon confirmed and extended to other species. In the early part of the 20th century, Harvard undergraduate Clarence Cook Little was conducting 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 ...
. Little and Castle collaborated closely with Abbie Lathrop who was a breeder of
fancy mice A fancy mouse (''Mus musculus domestica'') is a domesticated form of the house mouse (''Mus musculus''), one of many mice species, usually kept as a type of pocket pet. Fancy mice have also been specially bred for exhibiting, with shows being ...
and rats which she marketed to rodent hobbyists and keepers of exotic pets, and later began selling in large numbers to scientific researchers. Together they generated the DBA (Dilute, Brown and non-Agouti) inbred mouse strain and initiated the systematic generation of 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. The Jackson Laboratory in Bar Harbor, Maine is currently one of the world's largest suppliers of laboratory mice, at around 3 million mice a year. The laboratory is also the world's source for more than 8,000 strains of genetically defined mice and is home of the
Mouse Genome Informatics Mouse Genome Informatics (MGI) is a free, online database and bioinformatics resource hosted by The Jackson Laboratory, with funding by the National Human Genome Research Institute (NHGRI), the National Cancer Institute (NCI), and the Eunice Kenne ...
database.


Reproduction

Breeding onset occurs at about 50 days of age in both females and males, although females may have their first
estrus The estrous cycle (, originally ) is the set of recurring physiological changes that are induced by reproductive hormones in most mammalian therian females. Estrous cycles start after sexual maturity in females and are interrupted by anestrous ...
at 25–40 days. Mice are polyestrous and breed year round; ovulation is spontaneous. The duration of the
estrous cycle The estrous cycle (, originally ) is the set of recurring physiological changes that are induced by reproductive hormones in most mammalian therian females. Estrous cycles start after sexual maturity in females and are interrupted by anestro ...
is 4–5 days and lasts about 12 hours, occurring in the evening. Vaginal smears are useful in timed matings to determine the stage of the estrous cycle. Mating can be confirmed by the presence of a
copulatory plug A mating plug, also known as a copulation plug, sperm plug, vaginal plug, or sphragis (Latin, from Greek σφραγίς ''sphragis'', "a seal"), is gelatinous secretion used in the mating of some species. It is deposited by a male into a female g ...
in the vagina up to 24 hours post-copulation. The presence of sperm on a vaginal smear is also a reliable indicator of mating. The average gestation period is 20 days. A fertile postpartum estrus occurs 14–24 hours following
parturition Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause the muscular walls of the uterus to contract, expelling the f ...
, and simultaneous lactation and gestation prolongs gestation by 3–10 days owing to delayed implantation. The average
litter Litter consists of waste products that have been discarded incorrectly, without consent, at an unsuitable location. Litter can also be used as a verb; to litter means to drop and leave objects, often man-made, such as aluminum cans, paper cups ...
size is 10–12 during optimum production, but is highly strain-dependent. As a general rule,
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 ...
mice tend to have longer gestation periods and smaller litters than outbred and
hybrid Hybrid may refer to: Science * Hybrid (biology), an offspring resulting from cross-breeding ** Hybrid grape, grape varieties produced by cross-breeding two ''Vitis'' species ** Hybridity, the property of a hybrid plant which is a union of two dif ...
mice. The young are called pups and weigh at birth, are hairless, and have closed eyelids and ears. Pups are weaned at 3 weeks of age when they weigh about . If the female does not mate during the postpartum estrus, she resumes cycling 2–5 days post-weaning. Newborn males are distinguished from newborn females by noting the greater
anogenital distance Anogenital distance (AGD) is the distance from the midpoint of the anus to the genitalia, the underside of the vagina, the clitoris or the scrotum. It is considered medically significant for a number of reasons, in both humans and other animals ...
and larger
genital papilla The genital papilla is an anatomical feature of the external genitalia of some animals. In mammals In mammals, the genital papilla is a part of female external genitalia not present in humans, which appears as a small, fleshy flab of tissue. The p ...
in the male. This is best accomplished by lifting the tails of
littermate A litter is the live birth of multiple offspring at one time in animals from the same mother and usually from one set of parents, particularly from three to eight offspring. The word is most often used for the offspring of mammals, but can be use ...
s and comparing perinea.


Genetics and strains

Mice are mammals of the clade (a group consisting of an ancestor and all its descendants)
Euarchontoglires Euarchontoglires (synonymous with Supraprimates) is a clade and a superorder of mammals, the living members of which belong to one of the five following groups: rodents, lagomorphs, treeshrews, colugos, and primates. Evolutionary affinities wi ...
, which means they are amongst the closest non-
primate Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians ( monkeys and apes, the latter including ...
relatives of humans along with lagomorphs, treeshrews, and flying lemurs. Laboratory mice are the same species as the house mouse; however, they are often very different in behaviour and
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 ...
. There are hundreds of established
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 ...
, outbred, and transgenic strains. A ''
strain Strain may refer to: Science and technology * Strain (biology), variants of plants, viruses or bacteria; or an inbred animal used for experimental purposes * Strain (chemistry), a chemical stress of a molecule * Strain (injury), an injury to a mu ...
'', in reference to rodents, is a group in which all members are as nearly as possible genetically identical. In laboratory mice, this is accomplished through
inbreeding 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 ...
. By having this type of population, it is possible to conduct experiments on the roles of genes, or conduct experiments that exclude genetic variation as a factor. In contrast, outbred populations are used when identical genotypes are unnecessary or a population with genetic variation is required, and are usually referred to as ''stocks'' rather than ''strains''. Over 400 standardized, inbred strains have been developed. Most laboratory mice are hybrids of different subspecies, most commonly of ''Mus musculus domesticus'' and ''Mus musculus musculus''. Laboratory mice can have a variety of coat colours, including agouti, black and
albino Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino. Varied use and interpretation of the term ...
. Many (but not all) laboratory strains are inbred. The different strains are identified with specific letter-digit combinations; for example C57BL/6 and
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 ...
. The first such inbred strains were produced in 1909 by Clarence Cook Little, who was influential in promoting the mouse as a laboratory organism. In 2011, an estimated 83% of laboratory rodents supplied in the U.S. were C57BL/6 laboratory mice.


Genome

Sequencing of the laboratory mouse
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 ...
was completed in late 2002 using the C57BL/6 strain. This was only the second mammalian genome to be sequenced after humans. The haploid genome is about three billion base pairs long (3,000 Mb distributed over 19 autosomal chromosomes plus 1 respectively 2 sex chromosomes), therefore equal to the size of the human genome. Estimating the number of genes contained in the mouse genome is difficult, in part because the definition of a
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 ...
is still being debated and extended. The current count of primary coding genes in the laboratory mouse is 23,139. compared to an estimated 20,774 in humans.


Mutant and transgenic strains

Various
mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
strains of mice have been created by a number of methods. A small selection from the many available strains includes - * Mice resulting from ordinary
breeding Breeding is sexual reproduction that produces offspring, usually animals or plants. It can only occur between a male and a female animal or plant. Breeding may refer to: * Animal husbandry, through selected specimens such as dogs, horses, and ra ...
and
inbreeding 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 ...
: ** Non-obese diabetic (NOD) mice, which develop
diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...
. ** Murphy Roths large (MRL) mice, with unusual regenerative capacities ** Japanese waltzing mice, which walk in a circular pattern due to a mutation adversely affecting their inner
ear An ear is the organ that enables hearing and, in mammals, body balance using the vestibular system. In mammals, the ear is usually described as having three parts—the outer ear, the middle ear and the inner ear. The outer ear consists of ...
s ** Immunodeficient
nude mice A nude mouse is a laboratory mouse from a strain with a genetic mutation that causes a deteriorated or absent thymus, resulting in an inhibited immune system due to a greatly reduced number of T cells. The phenotype (main outward appearance) of ...
, lacking hair and a
thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...
: these mice do not produce
T lymphocyte A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s; therefore, they do not mount cellular immune responses. They are used for research in
immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see the ...
and transplantation. **
Severe combined immunodeficiency Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in diffe ...
(SCID) mice, with an almost completely defective
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...
** FVB mice, whose large litter sizes and large oocyte pronuclei expedite use in genetic research ** , which fail to recruit nutrient copper into milk causing pup death. It is caused by an
autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosom ...
recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
mutation '' tx'' which arose in an inbred. Theophilos et al. 1996 found this to be genetic and localized to chromosome 8, near the
centromere The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fibers ...
. * Transgenic mice, with foreign genes inserted into their genome: ** Abnormally large mice, with an inserted rat
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
gene ** Oncomice, with an activated
oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
, so as to significantly increase the incidence 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 ...
** Doogie mice, with enhanced NMDA receptor function, resulting in improved memory and learning * Knockout mice, where a specific gene was made inoperable by a technique known as gene knockout: the purpose is to study the function of the gene's product or to simulate a human disease ** Fat mice, prone to obesity due to a carboxypeptidase E deficiency ** Strong muscular mice, with a disabled
myostatin Myostatin (also known as growth differentiation factor 8, abbreviated GDF8) is a protein that in humans is encoded by the ''MSTN'' gene. Myostatin is a myokine that is produced and released by myocytes and acts on muscle cells to inhibit muscle ...
gene, nicknamed "mighty mice". Since 1998, it has been possible to clone mice from cells derived from adult animals.


Appearance and behaviour

Laboratory mice have retained many of the physical and behavioural characteristics of house mice; however, due to many generations of artificial selection, some of these characteristics now vary markedly. Due to the large number of strains of laboratory mice, it is impractical to comprehensively describe the appearance and behaviour of all of them; however, they are described below for two of the most commonly used strains.


C57BL/6

C57BL/6 mice have a dark brown, nearly black coat. They are more sensitive to noise and odours and are more likely to bite than the more docile laboratory strains such as
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 ...
. Group-housed C57BL/6 mice (and other strains) display barbering behaviour, in which the dominant mouse in a cage selectively removes hair from its subordinate cage mates. Mice that have been barbered extensively can have large bald patches on their bodies, commonly around the head, snout, and shoulders, although barbering may appear anywhere on the body. Both hair and vibrissae may be removed. Barbering is more frequently seen in female mice; male mice are more likely to display dominance through fighting. C57BL/6 has several unusual characteristics which make it useful for some research studies but inappropriate for others: It is unusually sensitive to pain and to cold, and analgesic medications are less effective in this strain. Unlike most laboratory mouse strains, the C57BL/6 drinks alcoholic beverages voluntarily. It is more susceptible than average to morphine addiction,
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...
, and age-related
hearing loss Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spoken ...
. When compared directly to BALB/c mice, C57BL/6 mice also express both a robust response to social rewards and empathy.


BALB/c

BALB/c is an
albino Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino. Varied use and interpretation of the term ...
laboratory-bred strain from which a number of common substrains are derived. With over 200 generations bred since 1920, BALB/c mice are distributed globally and are among the most widely used inbred strains used in
animal experimentation 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 ...
. BALB/c are noted for displaying high levels of anxiety and for being relatively resistant to diet-induced
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...
, making them a useful model for cardiovascular research. Male BALB/c mice are aggressive and will fight other males if housed together. However, the BALB/Lac substrain is much more docile. Most BALB/c mice substrains have a long reproductive life-span. There are noted differences between different BALB/c substrains, though these are thought to be due to
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...
rather than genetic contamination. The BALB/cWt is unusual in that 3% of progeny display true
hermaphroditism In reproductive biology, a hermaphrodite () is an organism that has both kinds of reproductive organs and can produce both gametes associated with male and female sexes. Many taxonomic groups of animals (mostly invertebrates) do not have s ...
.


Husbandry


Handling

Traditionally, laboratory mice have been picked up by the base of the tail. However, recent research has shown that this type of handling increases anxiety and aversive behaviour. Instead, handling mice using a tunnel or cupped hands is advocated. In behavioural tests, tail-handled mice show less willingness to explore and to investigate test stimuli, as opposed to tunnel-handled mice which readily explore and show robust responses to test stimuli.


Nutrition

In nature, mice are usually herbivores, consuming a wide range of fruit or grain.Mouse: Northwestern University Ecodome Information Page
/ref> However, in laboratory studies it is usually necessary to avoid biological variation and to achieve this, laboratory mice are almost always fed only commercial pelleted mouse feed. Food intake is approximately per of body weight per day; water intake is approximately per 100 g of body weight per day.


Injection procedures

Routes of administration A route of administration in pharmacology and toxicology is the way by which a medication, drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance i ...
of injections in laboratory mice are mainly subcutaneous,
intraperitoneal The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesothel ...
and intravenous. Intramuscular administration is not recommended due to small muscle mass. Intracerebral administration is also possible. Each route has a recommended injection site, approximate
needle gauge A hypodermic needle (from Greek ὑπο- (''hypo-'' = under), and δέρμα (''derma'' = skin)), one of a category of medical tools which enter the skin, called sharps, is a very thin, hollow tube with one sharp tip. It is commonly used w ...
and recommended maximum injected volume at a single time at one site, as given in the table below: To facilitate intravenous injection into the tail, laboratory mice can be carefully warmed under heat lamps to vasodilate the vessels.


Anaesthesia

A common regimen for
general anesthesia General anaesthesia (UK) or general anesthesia (US) is a medically induced loss of consciousness that renders the patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general ...
for the house mouse is
ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ...
(in the dose of 100 mg per kg body weight) plus xylazine (in the dose of 5–10 mg per kg), injected by the intraperitoneal route.Guidelines for Systemic Anesthetics (Mouse)
From Duke University and Medical Center – Animal Care & Use Program. Retrieved April 2011
It has a duration of effect of about 30 minutes.


Euthanasia

Approved procedures for euthanasia of laboratory mice include compressed gas, injectable barbiturate
anesthetics An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
, inhalable anesthetics, such as Halothane, and physical methods, such as cervical dislocation and decapitation. In 2013, the American Veterinary Medical Association issued new guidelines for induction, stating that a flow rate of 10% to 30% volume/min is optimal for euthanasing laboratory mice.2013 AVMA Guidelines for the Euthanasia of Animals
/ref>


Pathogen susceptibility

A recent study detected a murine
astrovirus Astroviruses are a type of virus that was first discovered in 1975 using electron microscopes following an outbreak of diarrhea in humans. In addition to humans, astroviruses have now been isolated from numerous mammalian animal species (and a ...
in laboratory mice held at more than half of the US and Japanese institutes investigated. Murine astrovirus was found in nine mice strains, including NSG, NOD-SCID, NSG-3GS, C57BL6-''Timp-3−/−'', uPA-NOG, B6J, ICR, Bash2, and
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 ...
, with various degrees of prevalence. The pathogenicity of the murine astrovirus was not known.


Legislation in research


United Kingdom

In the U.K., as with all other vertebrates and some invertebrates, any scientific procedure which is likely to cause "pain, suffering, distress or lasting harm" is regulated by the Home Office under the
Animals (Scientific Procedures) Act 1986 The Animals (Scientific Procedures) Act 1986, sometimes referred to as ASPA, is an Act of Parliament, Act of the Parliament of the United Kingdom (1986 c. 14) passed in 1986, which regulates the use of animals used for research in the UK. The Act ...
. U.K. regulations are considered amongst the most comprehensive and rigorous in the world. Detailed data on the use of laboratory mice (and other species) in research in the U.K. are published each year. In the U.K. in 2013, there were a total of 3,077,115 regulated procedures on mice in scientific procedure establishments, licensed under the Act.


United States

In the U.S., laboratory mice are not regulated under the Animal Welfare Act administered by the
USDA The United States Department of Agriculture (USDA) is the federal executive department responsible for developing and executing federal laws related to farming, forestry, rural economic development, and food. It aims to meet the needs of com ...
APHIS. However, the Public Health Service Act (PHS) as administered by the
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 ...
does offer a standard for their care and use. Compliance with the PHS is required for a research project to receive federal funding. PHS policy is administered by the Office of Laboratory Animal Welfare. Many academic research institutes seek accreditation voluntarily, often through the Association for Assessment and Accreditation of Laboratory Animal Care, which maintains the standards of care found within ''The Guide for the Care and Use of Laboratory Animals'' and the PHS policy. This accreditation is, however, not a prerequisite for federal funding, unlike the actual compliance.


Limitations

While mice are by far the most widely used animals in biomedical research, recent studies have highlighted their limitations. For example, the utility of rodents in testing for
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 ...
,
burn A burn is an injury to skin, or other tissues, caused by heat, cold, electricity, chemicals, friction, or ultraviolet radiation (like sunburn). Most burns are due to heat from hot liquids (called scalding), solids, or fire. Burns occur ma ...
s,
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
, stroke, ALS, Alzheimer's disease,
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 ...
,
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 ...
, multiple sclerosis,
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 ...
, and other illnesses has been called into question by a number of researchers. Regarding experiments on mice, 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 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, 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. In addition, the caging of laboratory animals may render them irrelevant models of human health because these animals lack day-to-day variations in experiences, agency, and challenges that they can overcome. The impoverished environments inside small mouse cages can have deleterious influences on biomedical results, especially with respect to studies of mental health and of systems that depend upon healthy psychological states. For example, researchers have found that many mice in laboratories are obese from excess food and minimal exercise, which alters their physiology and drug metabolism. Many laboratory animals, including mice, 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 are poorly designed, leading to questionable findings. 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 Montreal ( ; officially Montréal, ) is the second-most populous city in Canada and most populous ...
which suggests that mice handled by men rather than women showed higher stress levels. Another study in 2016 suggested that gut
microbiome 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 wel ...
s in mice may have an impact upon scientific research.


Market size

The worldwide market for gene-altered mice is predicted to grow to $1.59 billion by 2022, growing at a rate of 7.5 percent per year.


See also

*
Laboratory rat A laboratory rat or lab rat is a brown rat of the subspecies '' Rattus norvegicus domestica'' which is bred and kept for scientific research. While less commonly used for research than mice (see laboratory mouse), rats have served as an import ...
*
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 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 ...
*
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 ...
*
Animal Identification Animal identification using a means of marking is a process done to identify and track specific animals. It is done for a variety of reasons including verification of ownership, biosecurity control, and tracking for research or agricultural purpose ...
*
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 laboratory mice who orbited the Moon 75 times on Apollo 17 * Mouse models of colorectal and intestinal cancer * ''
Pinky and the Brain ''Pinky and the Brain'' is an American animated television series that was created by Tom Ruegger that premiered on Kids' WB on September 9, 1995. It was the first animated television series to be presented in Dolby Surround and the fourth col ...
'' *
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 ...
* ''
Monument to the laboratory mouse The ''Monument to the laboratory mouse'' is a sculpture in Novosibirsk' Akademgorodok, Siberia, Russia. It is located in a park in front of the Institute of Cytology and Genetics of the Russian Academy of Sciences, and was completed on July 1, 20 ...
''


References


Further reading

* *


External links

Taxonomy * http://www.findmice.org/ Genetics
Ensembl Mus musculus genome browser
from the
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 ...
Project
Vega Mus musculus genome browser
includes NOD mouse sequence and annotation Media
Pictures, movies and applets showing the anatomy of ''Mus musculus''
from www.digimorph.org

Study of male mouse "song" with mouse song recording (MP3), by Washington University Medical School *
Arkive
Photographs.Short text.
High-Resolution Brain Maps and Brain Atlases of ''Mus musculus''
Further reading

from the Louisiana Veterinary Medical Association
Nature Mouse Special 2002


by David G. Besselsen {{Authority control Cosmopolitan mammals House mouse Old World rats and mice Cruelty to animals Animal models