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Epigenetic inheritance at the agouti locus in the mouse
H D Morgan1, H G Sutherland, D I Martin
1Department of Biochemistry, University of Sydney, NSW, 2006, Australia.
Nature Genetics
|November 5, 1999
Summary
Maternal inheritance of epigenetic modifications occurs in mice, challenging the idea that only genetic traits pass to offspring. This epigenetic inheritance at the agouti locus influences offspring phenotype.
Area of Science:
- Genetics
- Epigenetics
- Mammalian reproduction
Background:
- Epigenetic modifications influence phenotype but are typically erased during germline transmission in mammals.
- The agouti locus in mice provides a model for studying epigenetic effects on phenotype, with variations linked to retrotransposon activity.
Purpose of the Study:
- To investigate the inheritance of epigenetic modifications at the agouti locus in mice.
- To determine if maternal epigenetic effects influence offspring phenotype beyond genetic inheritance.
Main Methods:
- Analysis of viable yellow (A(vy)/a) mice with retrotransposon insertions affecting agouti gene expression.
- Observation of phenotypic variation (coat color, obesity, diabetes) in relation to maternal phenotype.
- Experimental demonstration that the observed maternal effect is due to incomplete epigenetic erasure in the female germline.
Main Results:
- Epigenetic modifications at the agouti locus can be inherited across generations in mice.
- Maternal phenotype influences offspring phenotype, indicating a non-genetic inheritance mechanism.
- The inheritance is linked to incomplete epigenetic erasure of a silenced A(vy) allele in the female germline.
Conclusions:
- Epigenetic inheritance through the germline is possible in mammals, contrary to previous assumptions.
- Retrotransposon-mediated epigenetic modifications may be commonly inherited, impacting mammalian evolution.
- This finding has implications for understanding the transmission of complex traits and diseases.
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