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Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice
G L Wolff1, R L Kodell, S R Moore
1Division of Biochemical Toxicology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, Arkansas 72079-9502, USA. GWOLFF@NCTR.FDA.GOV
Summary
Maternal diet can influence offspring epigenetics. Methyl-supplemented diets in pregnant mice increased pseudoagouti phenotypes, promoting healthier, longer-lived offspring by altering agouti gene expression.
Area of Science:
- Epigenetics
- Developmental Biology
- Nutritional Science
Background:
- The 'viable yellow' (Avy/a) mouse model exhibits obesity, hyperinsulinemia, and reduced lifespan due to ectopic agouti gene expression.
- Avy/a mice display epigenetic mosaicism, with varying degrees of agouti overexpression leading to distinct phenotypes, including the lean, long-lived pseudoagouti form.
- Epigenetic phenotypes, including Avy expression, are known to be influenced by imprinting, strain, and maternal inheritance.
Purpose of the Study:
- To investigate the impact of maternal diet on the epigenetic regulation of agouti expression in Avy/a mice offspring.
- To determine if maternal dietary supplementation can alter the phenotypic expression of the Avy allele.
- To explore the role of maternal diet in modulating epigenetic inheritance and its effects on offspring health and longevity.
Main Methods:
- Pregnant a/a mice were fed methyl-supplemented diets.
- Offspring phenotypes were assessed for changes in coat color mottling, indicative of agouti gene expression.
- Epigenetic heritability of phenotypes was confirmed through maternal lineage tracking.
Main Results:
- Maternal feeding of methyl-supplemented diets resulted in increased agouti/black mottling in offspring, shifting towards the pseudoagouti phenotype.
- This dietary intervention demonstrated an alteration in the epigenetic regulation of agouti expression.
- Confirmatory evidence supported the maternal heritability of these diet-induced epigenetic changes.
Conclusions:
- Maternal diet, specifically methyl supplementation, can modulate epigenetic mechanisms controlling agouti gene expression in developing embryos.
- Dietary interventions during pregnancy may positively influence offspring health and longevity by altering epigenetic programming.
- The Avy/a mouse model serves as a valuable system for identifying maternal dietary factors that impact embryonic epigenetic regulation, particularly DNA methylation.