Page 1321 - Veterinary Immunology, 10th Edition

VetBooks.ir Immunodeficiencies of Mice

Many different genetic mutations have been shown to impair
immunity in mice. Some of these mutant mice are widely employed

in research investigating basic immunologic mechanisms.

Nude Mice

The best-known mouse model of immunodeficiency is the nude
mouse. Nude mice are a strain of hairless mice whose thymic

epithelial cells are nonfunctional as a result of a defect in the gene
for the transcription factor FoxN1. (Similar mutations have been
observed in rats, guinea pigs, calves, and cats.) Because their thymic
epithelial cells fail to function, the primitive thymus in nude mice

develops into cysts with walls of immature epithelial cells that do
not produce mature T cells. They do possess a limited number of
immature T cells and B cells so that a few lymphocytes may be
found in peripheral blood. Normal thymus grafts, by restoring

epithelial cell function, permit the T cells of nude mice to mature
and develop immune competence. Nude mice are deficient in
conventional cell-mediated immune responses, as reflected by
prolonged allograft survival and lack of responses to T cell

mitogens. Their IgG and IgA levels also are depressed, presumably
as a result of a loss of helper T cells.
Although nude mice show enhanced susceptibility to virus-
induced tumors, they fail to develop more than the normal level of

spontaneous tumors. This observation was, for many years, a major
objection to the immunological surveillance theory because if T cells
destroy tumors, T cell–deficient animals should have an increased
incidence of cancer. However, nude mice possess normal numbers

of NK cells, which may protect them in the absence of T cells.

Severe Combined Immunodeficiency Mice

SCID mice have very low numbers of B cells and T cells as a result
of a mutation that affects the differentiation of lymphoid stem cells.

Development of B cells is halted before expression of cytoplasmic or

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