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Whereas genetic factors are known to influence both susceptibility to carcinogens and the capacity to respond to specific antigenic stimuli, little is known regarding the influence of phenotype per se. With this in mind, we utilized (YS x VY)F1 hybrid mice consisting of genetically identical (Avy/a) but phenotypically distinct (mottled yellow and pseudoagouti) mice as well as congeneic (a/a) black mice to evaluate immunocompetence as a function of genotype and phenotype. Mottled yellow Avy/a mice, which are fat and have increased susceptibility to neoplasia, presented an immunologic profile characterized by decreased antibody response to the T-cell-dependent immunogen tetanus toxoid, enhanced antibody response to the T-cell-independent immunogen type III pneumococcal polysaccharide, decreased (unadjusted) rates of carbon clearance, and increased levels of serum IgA. In contrast, pseudoagouti Avy/a mice were immunologically comparable to black a/a mice. The data demonstrate that differences in phenotypic expression between genetically identical mice may significantly alter immune function.

Differential effects of the mottled yellow and pseudoagouti phenotypes on immunocompetence in Avy/a mice.