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Mouse in Science
WHY MICE?
see also Animal Use Statistics
Among the animals used in research, teaching, and testing, mice comprise a majority of all experimental mammals. The remarkable genetic similarity of mice to humans, combined with great convenience, perhaps accounts for mice so often being the experimental model of choice in research. Mice also are used to test new procedures and drugs for safety, as required by an array of federal regulations. Another primary use of mice is for the production of biological reagents, such as monoclonal antibodies and vaccines.
The Handiest Mammal
Besides being genetically similar to humans, mice are small and
inexpensive to maintain. Their short life span and rapid reproductive rate make
it possible to study disease processes in many individuals throughout their life
cycle.
How are They Used?
* Testing: Mice are used to evaluate the safety of new
chemicals or products such as household cleaners and pesticides that may be
potentially toxic to humans. Mice are also used to assess the safety of drugs
and vaccines made for medical use.
Toxicity tests are performed to measure the effects of limited or repeated, long-term exposure of an animal to a particular substance. Other tests measure the extent to which the substance damages cells and causes cancer, mutations in DNA, and birth defects.
The LD50 test, developed in 1927, made it possible to
derive a numerical index of toxicity reflecting the lethal dose of a test
substance. The test substance was administered to the animal by feeding,
injecting, inhalation, or application to the skin. A major drawback to the LD50
test was that it used large numbers of animals. Although it is one of the most
well known toxicity tests, it is being replaced by tests using fewer animals
that do not require death of the animal as an endpoint.
* Biomedical Research:
Mice are used in biomedical research as models of human beings in
order to understand the human body, determine the effects of diseases, and
develop treatments for diseases. The nude mouse is used to study cancer. Its
immunodeficient status allows human tumors to be grafted onto the mouse without
rejection. This procedure allows for the study of specific human cancers and the
testing of new treatments.
Education and Teaching:
Mice and other mammals are used in biological, medical and
veterinary education. High school and college students commonly perform
dissections on cats, fetal pigs, or other animals to learn about anatomy.
Students in medical and veterinary schools use animals to learn and practice
surgical and other medical procedures. Far fewer mice and other animals are used
in teaching than in testing and research.
Legislation
The
United States Animal Welfare Act as revised in 1985 includes most mammals, but
excludes laboratory rats and mice. Research institutions voluntarily can seek
accreditation by the Association for Assessment and Accreditation of Laboratory
Animal Care International (AAALAC). Accreditation assures that an institution is
in conformance with the Guide for the Care and Use of Laboratory Animals, which applies to all laboratory animals, including rats and mice. This
conformance with the Guide is a requirement for funding by many federal
agencies, such as NIH. Hence, most academic institutions seek accreditation and
provide the same level of oversight for the care of mice as for other
mammals.
For industries or testing facilities that do not seek
funding and house only rats and mice, legislation and accreditation requirements
do not apply. These institutions would only retain an institutional animal care
and use committee as a proactive measure to assure optimal animal welfare, not
as a regulatory requirement. One drawback of mice not being regulated is that no
accurate figures are available concerning the numbers of mice used in the United
States.
How Many?
Without
systematic reporting in the United States, accurate estimates of numbers of mice
used are not available. However, Great Britain used 1,448,960 mice in 1992, 49%
of their total vertebrate animals used. In comparable figures from the
Netherlands, 378,834 mice were 43% of all animals used. Rough estimates in the
United States range upwards from 6 million mice, presumably accounting for at
least half of all mammals used per year.
Quality of Life
Induced genetic defects and research procedures sometimes cause
pain and suffering to laboratory mice that may be somewhat alleviated by
appropriate analgesia and anesthesia. Enhancing the quality of life for mice may
partially offset some of their discomfort. For example, living in social groups
would be a more normal situation than solitary housing. Caregivers also can
enrich the physical environments of mice by considering the housing. Mice
provided with hardwood shavings burrow and build nests. Placing hay or straw on
racks above cages allows mice to pull material into the cage and arrange nests.
Plastic tubes offer an artificial burrow space, perhaps shielding mice from
illumination that may be too bright. Simple enrichments such as these can
provide mice some control over their environment.
One complication is that immunodeficient mice require
sterile environments. All cage materials used for them, including bedding, food
and water, must be autoclaved for sterilization before use. Thus, offering an
improved quality of life requires more effort and cost when dealing with those
mice that are especially valuable for studies of human diseases.
Alternatives
Alternatives to using mice in testing, research and education
involve the concepts of replacement, reduction and refinement. The numbers used
can be reduced, and the procedures can be more refined to provide mice a better
quality of life or reduce their pain or suffering. Whenever possible, the use of
animals can be replaced with improved methods.
* Testing and Research
Human studies:Humans who are injured or sick can be studied during recovery and treatment.
In vitro techniques:Tissue and cell cultures can be used to screen certain chemicals before using whole animal toxicity tests.
Mathematical or computer modelling:A simplified version of an organism that sometimes helps in understanding complex systems; variables are entered into a computer and outcomes considered through a model.
Use of less sentient organisms:Invertebrates, such as
jellyfish, can be used to detect toxic qualities of chemicals; plants or plant
cells can be used to test phototoxins.
Education
Computer simulations:Virtual software on anatomy replaces dissection.
Demonstration and clinical participation:</UL
Mentoring is expanded in laboratory and clinical settings.
Ethical Questions
*
Should it be possible to patent a mouse strain that carries a gene for a human
disease?
* Do mice experiencing adverse circumstances, such as radiation or general discomfort, merit compensatory enhancements in their care?
* Should there be limits to the extent of induced genetic pathology?
Mouse by Design: Some Strain Types
Inbred: Mice that are predisposed to getting a
certain disease or genetic defect; they are genetically identical due to
inbreeding.
Transgenic: Mice that have been genetically engineered and altered by injection of one or more genes, such as human breast cancer.
Immunodeficient: Mice used in cancer and AIDS research that have minimal immune function, including nude mice and mice with severe combined immune deficiency (SCID).
Knockout: Mice that are engineered to lack a specific gene.
Germfree: Mice that are free from all detectable viruses, bacteria and parasites.
Lynette A. Hart, Professor, SVM:PHR
Amy Dassler, Undergraduate intern 1996
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