The laboratory mouse or lab mouse is a small mammal of the order
Rodent
Rodents (from Latin , 'to gnaw') are mammals of the Order (biology), 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 roden ...
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 ...
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' ...
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, Ne ...
''. 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 worki ...
,
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 chemic ...
,
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 betwe ...
,
medicine
Medicine is the science and Praxis (process), practice of caring for a patient, managing the diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, and Health promotion ...
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 ...
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 affinitie ...
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'').
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 prope ...
used them for his studies on reproduction and blood circulation and
Robert Hooke
Robert Hooke FRS (; 18 July 16353 March 1703) was an English polymath active as a scientist, natural philosopher and architect, who is credited to be one of two scientists to discover microorganisms in 1665 using a compound microscope that h ...
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 e ...
and
Antoine Lavoisier
Antoine-Laurent de Lavoisier ( , ; ; 26 August 17438 May 1794), CNRS ( respiration. 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 wa ...
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
Lucien Claude Marie Julien Cuénot (; 21 October 1866 – 7 January 1951) was a French biologist. In the first half of the 20th century, Mendelism was not a popular subject among French biologists. Cuénot defied popular opinion and shirked the “ ...
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. Little and Castle collaborated closely with Abbie Lathrop who was a breeder of fancy mice 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
The Jackson Laboratory (often abbreviated as JAX) is an independent, non-profit biomedical research institution which was founded by a eugenicist. It employs more than 3,000 employees in Bar Harbor, Maine; Sacramento, California; Farmington, Con ...
in
Bar Harbor, Maine
Bar Harbor is a resort town on Mount Desert Island in Hancock County, Maine
Maine () is a U.S. state, state in the New England and Northeastern United States, Northeastern regions of the United States. It borders New Hampshire to the wes ...
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 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 p ...
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 anestr ...
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 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
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 p ...
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 mice tend to have longer gestation periods and smaller litters than
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 useful ...
and hybrid 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 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 littermates 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 affinitie ...
, which means they are amongst the closest non-
primate
Primates are a diverse order (biology), order of mammals. They are divided into the Strepsirrhini, strepsirrhines, which include the lemurs, galagos, and lorisids, and the Haplorhini, haplorhines, which include the Tarsiiformes, tarsiers and ...
relatives of humans along with
lagomorphs
The lagomorphs are the members of the taxonomic order Lagomorpha, of which there are two living families: the Leporidae (hares and rabbits) and the Ochotonidae (pikas). The name of the order is derived from the Ancient Greek ''lagos'' (λαγ� ...
,
treeshrew
The treeshrews (or tree shrews or banxrings) are small mammals native to the tropical forests of South and Southeast Asia. They make up the entire order Scandentia, which split into two families: the Tupaiidae (19 species, "ordinary" treeshrew ...
s, and
flying lemurs
Colugos () are arboreal gliding mammals that are native to Southeast Asia. Their closest evolutionary relatives are primates. There are just two living species of colugos: the Sunda flying lemur (''Galeopterus variegatus'') and the Philippine fl ...
.
Laboratory mice are the same species as the
house mouse
The house mouse (''Mus musculus'') is a small mammal of the order Rodentia, characteristically having a pointed snout, large rounded ears, and a long and almost hairless tail. It is one of the most abundant species of the genus ''Mus''. Althoug ...
; however, they are often very different in
behaviour
Behavior (American English) or behaviour ( British English) is the range of actions and mannerisms made by individuals, organisms, systems or artificial entities in some environment. These systems can include other systems or organisms as w ...
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 chemic ...
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 useful ...
, and
transgenic
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 the ...
strains. A '' strain'', 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 an ...
. 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
genotype
The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
s 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
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 w ...
and BALB/c. 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 ...
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 rab ...
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 an ...
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 f ...
.
**
Murphy Roths large Murphy Roths large (MRL/MpJ) is a strain of laboratory mouse developed in 1999 at The Wistar Institute in Philadelphia, Pennsylvania. Originally bred for autoimmune disease research, it was discovered to have remarkable tissue regeneration abiliti ...
(MRL) mice, with unusual regenerative capacities
**
Japanese waltzing mice
The Japanese house mouse or Japanese wild mouse (''Mus musculus molossinus'') is a type of house mouse that originated in Japan. Genetically, it is a hybrid between the southeastern Asian house mouse ('' M. m. castaneus'') and the eastern European ...
, which walk in a circular pattern due to a mutation adversely affecting their inner ears
**
Immunodeficient
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors tha ...
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 rec ...
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 ther ...
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 dif ...
(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 Tumor immunology, cancer cells and objects such ...
**
FVB mice FVB is an albino, inbred laboratory mouse strain that is named after its susceptibility to Friend leukemia virus B.
History
This strain was produced from mice established at the National Institutes of Health in 1935. In 1966, mice from this fo ...
, 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 autosomes ...
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 ...
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
A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse (''Mus musculus'') that has had its genome altered through the use of genetic engineering techniques. Genetically modified mice are commonly used for research or ...
, 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 ...
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 bl ...
**
Doogie mice
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...
, with enhanced
NMDA receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...
function, resulting in improved memory and learning
* Knockout mice, where a specific gene was made inoperable by a technique known as
gene knockout
A gene knockout (abbreviation: KO) is a genetic technique in which one of an organism's genes is made inoperative ("knocked out" of the organism). However, KO can also refer to the gene that is knocked out or the organism that carries the gene kno ...
: 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
Clone or Clones or Cloning or Cloned or The Clone may refer to:
Places
* Clones, County Fermanagh
* Clones, County Monaghan, a town in Ireland
Biology
* Clone (B-cell), a lymphocyte clone, the massive presence of which may indicate a pathologi ...
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.
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
Vibrissae (; singular: vibrissa; ), more generally called Whiskers, are a type of stiff, functional hair used by mammals to sense their environment. These hairs are finely specialised for this purpose, whereas other types of hair are coarse ...
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
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
medications are less effective in this strain. Unlike most laboratory mouse strains, the C57BL/6 drinks
alcoholic beverage
An alcoholic beverage (also called an alcoholic drink, adult beverage, or a drink) is a drink that contains ethanol, a type of alcohol that acts as a drug and is produced by fermentation of grains, fruits, or other sources of sugar. The c ...
s 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 ...
, 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 la ...
. 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 ...
, 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 or viral replication, m ...
rather than genetic contamination. The BALB/cWt is unusual in that 3% of progeny display true hermaphroditism.
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
herbivore
A herbivore is an animal anatomically and physiologically adapted to eating plant material, for example foliage or marine algae, for the main component of its diet. As a result of their plant diet, herbivorous animals typically have mouthp ...
s, 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.
subcutaneous Subcutaneous may refer to:
* Subcutaneous injection
* Subcutaneous tissue
The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The ...
, intraperitoneal 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 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
Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...
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
Euthanasia (from el, εὐθανασία 'good death': εὖ, ''eu'' 'well, good' + θάνατος, ''thanatos'' 'death') is the practice of intentionally ending life to eliminate pain and suffering.
Different countries have different eut ...
of laboratory mice include compressed gas, injectable
barbiturate
Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as ...
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
The American Veterinary Medical Association (AVMA), founded in 1863, is a not-for-profit association representing more than 99,500 veterinarians in the US.
The AVMA provides information resources, continuing education opportunities, publicati ...
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 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
Bash or BASH may refer to:
Arts and entertainment
* ''Bash!'' (Rockapella album), 1992
* ''Bash!'' (Dave Bailey album), 1961
* '' Bash: Latter-Day Plays'', a dramatic triptych
* ''BASH!'' (role-playing game), a 2005 superhero game
* "Bash" ('' ...
, and BALB/C, 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. 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
''Aphis'' is a genus of insects in the family Aphididae containing at least 600 species of aphids. It includes many notorious agricultural pests, such as the soybean aphid '' Aphis glycines''. Many species of ''Aphis'', such as '' A. coreopsidis ...
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
The federal government of the United States (U.S. federal government or U ...
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 foll ...
,
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 mainl ...
s,
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
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 bl ...
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
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 (1849 ...
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 in ...
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 th ...
, 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 in ...
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 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 oth ...
, 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 fou ...
, 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
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
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 useful ...
, 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, Canada. Founded in 1821 by royal charter granted by King George IV,Frost, Stanley Brice. ''McGill Universit ...
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 we ...
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
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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 ...
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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 ...
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 ...
, five laboratory mice who orbited the Moon 75 times on Apollo 17
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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 enable ...
* ''
Pinky and the Brain
''Pinky and the Brain'' is an American Animated series, 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 Pro Logic, D ...
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 ...