Laboratory mouse
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.
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".
[2] 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.
[2] 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.
[5] 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.
[7] 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.
Rodentia (rodents) Lagomorpha (rabbits, hares, pikas) Scandentia (treeshrews) Dermoptera (flying lemurs) Primates (†Plesiadapiformes, Strepsirrhini, Haplorrhini) Laboratory mice are the same species as the house mouse; however, they are often very different in behaviour and physiology.
The first such inbred strains were produced in 1909 by Clarence Cook Little, who was influential in promoting the mouse as a laboratory organism.
A small selection from the many available strains includes - Since 1998, it has been possible to clone mice from cells derived from adult animals.
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.
However, it is now known that this is more of a stereotypical behaviour triggered by stress, comparable to trichotillomania in humans or feather plucking in parrots.
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.
[46] BALB/c are noted for displaying high levels of anxiety and for being relatively resistant to diet-induced atherosclerosis, making them a useful model for cardiovascular research.
The mice exhibit main characteristics of Alzheimer's disease (AD), such as increased generation of amyloid fibrils with aging, plaque formation, and impaired hippocampus learning and memory.
[55] The absence of cell death suggests that changes in typical cellular signaling cascades involved in learning and synaptic plasticity are probably linked to the memory phenotype.
Associative learning impairments are exacerbated when Tg2576 mice are crossed with PS1 transgenic animals that possess the A246E FAD mutation.
[56] This lends credence to the theory that AD pathogenesis is influenced by the interplay between APP and PS-1 gene products.
[65] In 2013, the American Veterinary Medical Association issued new guidelines for CO2 induction, stating that a flow rate of 10% to 30% volume/min is optimal for euthanasing laboratory mice.
[66] A recent study detected a murine astrovirus in laboratory mice held at more than half of the US and Japanese institutes investigated.
[67] 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, with various degrees of prevalence.
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.
[73] 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, 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.
[89] 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.
[90] 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.
[91] Many laboratory animals, including mice, are chronically stressed, which can also negatively affect research outcomes and the ability to accurately extrapolate findings to humans.
Examples of hidden bias include a 2014 study from McGill University which suggests that mice handled by men rather than women showed higher stress levels.
