Prenatal determination of obesity, tumor susceptibility, and coat color pattern in viable yellow (Avy/a) mice

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Abstract
Maturity-onset obesity and elevated circulating Insulin levels are characteristic of some, but not all, mice bearing the viable yellow mutation (Avy) at the agouti locus. The expression of the Avy/a genotype in individual mice, which become obese and which remain lean is determined during prenatal development by as yet unidentified conditions In the dam's reproductive tract. One Avy/a phenotype is identified by a mottled yellow coat and characterized by adult obesity, elevated circulating insulin levels, and impaired glucose tolerance. These mice are notably more susceptible to hyperplasia and neoplasia. The alternative Avy/a phenotype has a pseudoagoutl coat, remains lean, is normoinsulinemic and normoglycemic, and in numerous other characteristics resembles congeneic lean black (a/a) littermates. Obese mottled yellow and lean pseudoagouti Avy/a mice differ in capacity to support the growth of ascltes cells, In the growth response to castration, and in hepatic glutathione S-transferase activity, erythrocyte fragility, Immune function, and susceptibility to Plasmodium yoeill pathogenesis. Our working hypothesis is that the constellation of characteristics, except coat color pattern, which differentiate the obese yellow mice from their lean littermates, is largety a consequence of the elevated circulating insuiln levels that induce increased lipogenesis and decreased lipoiysis, increased DNA and protein synthesis, increased mitosis in sensitive tissues, and Increased proliferation of transformed cells.