Nude mouse

  A nude mouse is a genetic mutant that has a deteriorated or removed thymus gland, resulting in an inhibited immune system due to a greatly reduced number of T cells. The phenotype, or main outward appearance of the mouse is a lack of body hair, which gives it the "nude" nickname. The nude mouse is valuable to research because it can receive many different types of tissue and tumor grafts, as it mounts no rejection response. These xenografts are commonly used in research to test new methods of imaging and treating tumors. The genetic basis of the nude mouse mutation is a disruption of the FOXN1 gene [1][2].

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Nomenclature

The nomenclature for the nude mouse has changed several times since their discovery. Originally they were described as nu and this was updated to Hfh11nu when the mutated gene was identified as a mutation in the HNF-3/forkhead homolog 11 gene. Then in 2000 the gene responsible for the mutation was identified as a member of the Fox gene family and the nomenclature was updated to Foxn1nu.

History and significance

Nude mice have been bred since at least 1937.^[1] Because it lacks a thymus, nude mice cannot generate mature T lymphocytes. Therefore they are unable to mount most types of immune responses, including:

1. antibody formation that requires CD4+ helper T cells
2. cell-mediated immune responses, which require CD4+ and/or CD8+ T cells
3. delayed-type hypersensitivity responses (require CD4+ T cells)
4. killing of virus-infected or malignant cells (requires CD8+ cytotoxic T cells)
5. graft rejection (requires both CD4+ and CD8+ T cells)

Because of the above features, nude mice have served in the laboratory to gain insights into the immune system, leukemia, solid tumors, AIDS and other forms of immune deficiency as well as leprosy. Moreover, the absence of functioning T cells prevents nude mice from rejecting not only allografts, but they cannot even reject xenografts; that is, grafts of tissue from another species.

Genetics

To create an athymic mouse, the researcher may remove genetic material from chromosome 11 which harbors the gene for Foxn1; alternatively, one could simply remove the thymus from the mouse within 24 hours of birth. Usually, the latter method is preferred as it is economically feasible and does not rely on genetic processes, including radioimmunoassays, which are often unreliable.

Athymic mice are most often bred rather than produced by either of the processes mentioned above. Since nude females have underdeveloped mammary glands and are unable to effectively nurse their young, nude males are bred with heterozygous females.

Nobel Prize

The concept of a "nude mouse" is the brainchild of Rosalyn Yalow. In 1977, she was awarded half the Nobel Prize for Medicine, for the development of the radioimmunoassays, mentioned above.

References

• The Nude Mouse in Experimental and Clinical Research (Vol.1). Fogh, J; Giovanella, B.C.(eds) Academic Press, 1978, ISBN 0-12-261860-2
• The Nude Mouse in Experimental and Clinical Research (Vol.2). Fogh, J; Giovanella, B.C.(eds) Academic Press, 1982, ISBN 0-12-261862-9

See also

• Skinny pig
• Earmouse