Nude Athymic Mice

A genetic trait designated nu, which is controlled by a recessive gene on chromosome 11, was discovered in certain mice. Mice homozygous for this trait (nu/nu) are hairless and have a vestigial thymus (Figure 19-5). Heterozygotic, nu/+, litter mates have hair and a normal thymus. It is not known whether the hairlessness and the thymus defect are caused by the same gene. It is possible that two very closely linked genes control these defects, which, although unrelated, appear together in this mutant mouse. A gene that controls development may be involved, since the pathway that leads to the differential development of the thymus is related to the one that controls the skin epithelial cells. The nu/nu mouse cannot easily survive; under normal conditions, the mortality is 100% within 25 weeks and 50% die within the first two weeks after birth. Therefore, when these animals are to be used for experimental purposes, they must be maintained under conditions that protect them from infection. Precautions include use of sterilized food, water, cages, and bedding. The cages are protected from dust by placing them in a laminar flow rack or by the use of air filters fitted over the individual cages.

Nude mice lack cell-mediated immune responses, and they are unable to make antibodies to most antigens. The

A nude mouse (nu/nu). This defect leads to absence of a thymus or a vestigial thymus and cell-mediated im


A nude mouse (nu/nu). This defect leads to absence of a thymus or a vestigial thymus and cell-mediated im munodeficiency. [Courtesy of the Jackson Laboratory, Bar Harbor, Maine]

immunodeficiency in the nude mouse can be reversed by a thymic transplant. Because they can permanently tolerate both allografts and xenografts, they have a number of practical experimental uses. For example, hybridomas or solid tumors from any origin may be grown as ascites or as implanted tumors in a nude mouse. It is known that the nude mouse does not completely lack T cells; rather, it has a limited population that increases with age. The source of these T cells is not known; an intriguing possibility is that there is an extrathymic source of mature T cells. However, it is more likely that the T cells arise from the vestigial thymus. The majority of cells in the circulation of a nude mouse carry T-cell receptors of the 78 type instead of the ap type that prevails in the circulation of a normal mouse.

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