The laboratory mouse or lab mouse is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory animal sources for these mice are usually of the species Mus musculus. They are the most commonly used mammalian research model and are used for research in genetics, physiology, psychology, medicine and other scientific disciplines. Mice belong to the Euarchontoglires 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. Lab mice are sold at pet stores for snake food and can also be kept as pets.
Other mouse species sometimes used in laboratory research include two American species, the white-footed mouse (Peromyscus leucopus) and the eastern deer mouse (Peromyscus maniculatus).
History as a biological model
Mice have been used in biomedical research since the 17th century, when William Harvey 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."The house mouse as a laboratory model: a historical perspective". pp. 9–13. in: During the 18th century, Joseph Priestley and Antoine Lavoisier both used mice to study respiration. In the 19th century, Gregor Mendel 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. Little and Castle collaborated closely with Abbie Lathrop, 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 in Bar Harbor, Maine is currently one of the world's largest suppliers of laboratory mice, supplying 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 at 25–40 days. Mice are polyestrous and breed year round; ovulation is spontaneous. The duration of the estrous cycle 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 occurs 14–24 hours following parturition, and simultaneous lactation and gestation prolongs gestation by 3–10 days, owing to delayed implantation. The average litter size is 10–12 during optimum production, but this is highly strain-dependent. In general, inbred mice tend to have longer gestation periods and smaller litters than outbred 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 their greater anogenital distance and larger genital papilla. This is usually observed 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, which means they are amongst the closest non-primate 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. There are hundreds of established inbred, outbred, and transgenic 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. 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. 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. 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 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 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 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 and inbreeding: Non-obese diabetic (NOD) mice, which develop diabetes mellitus type 1. 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 ears Immunodeficient nude mice, lacking hair and a thymus: these mice do not produce T lymphocytes; therefore, they do not mount cellular immune responses. They are used for research in immunology and transplantation. Severe combined immunodeficiency (SCID) mice, with an almost completely defective immune system 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 recessive mutation tx which arose in an inbred. Theophilos et al. 1996 found this to be genetic and localized to chromosome 8, near the centromere. Transgenic mice, with foreign genes inserted into their genome: Abnormally large mice, with an inserted rat growth hormone gene Oncomice, with an activated oncogene, so as to significantly increase the incidence of cancer 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 Obese mice, prone to obesity due to a carboxypeptidase E deficiency Strong muscular mice, with a disabled myostatin gene, nicknamed "mighty mice".
Since 1998, it has been possible to clone mice from cells derived from adult animals.
Commonly used inbred strains
There are many strains of mice used in research, however, inbred strains are usually the animals of choice for most fields. Inbred mice are defined as being the product of at least 20 generations of brother X sister mating, with all individuals being derived from a single breeding pair.
Inbred mice have several traits that make them ideal for research purposes. They are isogenic, meaning that all animals are nearly genetically identical. Approximately 98.7% of the genetic loci in the genome are homozygous, so there are probably no "hidden" recessive traits that could cause problems. They also have very unified phenotypes due to this stability.
Many inbred strains have well documented traits that make them ideal for specific types of research. The following table shows the top 10 most popular strains according to Jackson Laboratories. + Common inbred strains of laboratory mice available from Jackson Laboratories Strain Coat color Common research uses Total Pubmed publications referencing the strain as of April 19, 2023 C3HeB/FeJ Agouti Immunology, inflammation, autoimmunity 482 NOD/ShiLtJ Albino Autoimmune type 1 diabetes 105 DBA/1J Dilute brown Rheumatoid arthritis 445 BALB/cByJ Albino Cancer, cardiovascular, immunology 628 DBA/2J Dilute brown Cardiovascular, dermatology, developmental biology 2,722 C3H/HeJ Agouti Cancer, cardiovascular, hematology 4,037 C57BL/6J Black General purpose, background 25,723 SJL/J Albino Cancer, cardiovascular, dermatology 1,448 FVB/NJ Albino Immunology, inflammation, autoimmunity 350 129S1/SvImJ Agouti Targeted mutations, cancer 222
Jackson Labs DO project
The Jackson Labs DO (Diversity Outbred) project is a mouse breeding program using multiple inbred founder strains to create a genetically diverse population of mice for use in scientific research.
These mice are designed for fine genetic mapping, and capture a large portion of the genetic diversity of the mouse genome.
This project has resulted in over 1,000 genetically diverse mice which have been used to identify genetic factors for diseases such as obesity, cancer, diabetes, and alcohol use disorder.
+ Founder strains used in the DO project Strain Derivation Subspecies origin Coat color Common research uses Total Pubmed publications referencing the strain as of April 19, 2023 A/J Laboratory Mus musculus domesticus Albino Cancer, immunology 5,500 C57BL/6J Laboratory Mus musculus domesticus Black General purpose, background 25,723 129S1/SvImJ Laboratory Mus musculus domesticus Agouti Targeted mutations, cancer 222 NOD/ShiLtJ Laboratory Mus musculus domesticus Albino Autoimmune type 1 diabetes 105 NZO/HILtJ Laboratory Mus musculus domesticus Agouti Obesity 11 CAST/EiJ Wild-derived Mus musculus castaneus Agouti Crossbreeding heterozygous F1 hybrids, genetic mapping 154 PWK/PhJ Wild-derived Mus musculus musculus Agouti Genetic mapping 52 WSB/EiJ Wild-derived Mus musculus domesticus Agouti with head blaze, greyish coat
Genetic mapping, evolution 65
Appearance and behaviour