Genetic Modification of Homeostatic Regulation in the Mouse

Abstract

A single genotype in the mouse, Avy/a, induces a continuum of coat color phenotypes ranging from clear yellow through all degrees of intermixture of yellow, black, and agouti hairs to complete agouti. This range of phenotypes can be divided into two physiologically distinct classes, mottled yellow and agouti. The proportion of the agouti phenotype among Avy/a mice is determined by the background genotype and varies from 12%-58% among the stocks observed. Mottled yellow Avy/a mice exhibit higher serum insulin levels, maintain the same rate of liver weight gain in spite of castration, stimulate growth of allogeneic tumor cells, and gain weight more rapidly than black a/a mice. In contrast, the agouti Avy/a mice resemble their black a/a sibs in these attributes. These and other data suggest that the agouti locus may affect the concentration of a regulatory entity of importance in many metabolic processes. While the basic concentration of this factor is probably determined by the strain genome, mutations at the agouti locus appear to alter it.