Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice.

TLDR

Avy/a mice exhibit epigenetic mosaicism in agouti expression, with yellow phenotypes linked to obesity, hyperinsulinemia, cancer susceptibility, and reduced lifespan, whereas pseudoagouti mice are lean, healthy, and longer lived. The study aims to use this system to identify maternal factors that modulate epigenetic mechanisms, particularly DNA methylation, during embryonic development. Maternal methyl‑supplemented diets during pregnancy shift offspring agouti expression toward the pseudoagouti phenotype, confirming maternal epigenetic inheritance and indicating that maternal diet can improve offspring health and longevity.

Abstract

'Viable yellow' (Avy/a) mice are larger, obese, hyperinsulinemic, more susceptible to cancer, and, on average, shorter lived than their non-yellow siblings. They are epigenetic mosaics ranging from a yellow phenotype with maximum ectopic agouti overexpression, through a continuum of mottled agouti/yellow phenotypes with partial agouti overexpression, to a pseudoagouti phenotype with minimal ectopic expression. Pseudoagouti Avy/a mice are lean, healthy, and longer lived than their yellow siblings. Here we report that feeding pregnant black a/a dams methyl-supplemented diets alters epigenetic regulation of agouti expression in their offspring, as indicated by increased agouti/black mottling in the direction of the pseudoagouti phenotype. We also present confirmatory evidence that epigenetic phenotypes are maternally heritable. Thus Avy expression, already known to be modulated by imprinting, strain-specific modification, and maternal epigenetic inheritance, is also modulated by maternal diet. These observations suggest, at least in this special case, that maternal dietary supplementation may positively 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 developing embryos.