MATERNAL EPIGENETICS AND METHYL SUPPLEMENTS AFFECT AGOUTI GENE-EXPRESSION IN A(VY) A MICE/

'Viable yellow' (A(vy)/alpha) mice are larger, obese, hyperinsulinemic , more susceptible to cancer, and, on average, shorter lived than thei r non-yellow siblings. They are epigenetic mosaics ranging from a yell ow phenotype with maximum ectopic agouti overexpression, through a con tinuum of mottled agouti/yellow phenotypes with partial agouti overexp ression, to a pseudoagouti phenotype with minimal ectopic expression. Pseudoagouti A(vy)/a mice are lean, healthy, and longer lived than the ir yellow siblings. Here we report that feeding pregnant black a/a dam s methyl-supplemented diets alters epigenetic regulation of agouti exp ression in their offspring, as indicated by increased agouti/black mot tling in the direction of the pseudoagouti phenotype, We also present confirmatory evidence that epigenetic phenotypes are maternally herita ble. Thus A(vy) expression, already known to be modulated by imprintin g, strain-specific modification, and maternal epigenetic inheritance, is also modulated by maternal diet. These observations suggest, at lea st in this special case, that maternal dietary supplementation may pos itively affect health and longevity of the offspring, Therefore, this experimental system should be useful for identifying maternal factors that modulate epigenetic mechanisms, especially DNA methylation, in de veloping embryos.