ARS | Publication request: MATERNAL DIETARY METHYL DONOR SUPPLEMENTATION OF "AXIN(FU)/+" MICE PREVENTS TAIL KINKS BY TAIL-SPECIFIC CPG HYPERMETHYLATION AT "AXIN(FU)"

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: March 7, 2006
Publication Date: April 1, 2006
Citation: Waterland, R.A., Lin, J-R., Smith, C.A., Tahiliani, K. 2006. Maternal dietary methyl donor supplementation of "Axin(Fu)/+" mice prevents tail kinks by tail-specific CpG hypermethylation at "Axin(Fu)" [abstract]. The Federation of American Societies for Experimental Biology Conference: Advancing the Biomedical Frontier, April 1-5, 2006, San Francisco, California. 20(5):Part II, p. A1339.

Technical Abstract: Methyl donor supplementation of the maternal diet alters coat color phenotype of viable yellow agouti "(A[vy]/a)" offspring by a locus-specific increase in CpG methylation. To test the hypothesis that metastable epialleles such as "A[vy]" are, in general, susceptible to early nutritional influences on the establishment of epigenotype, we determined whether maternal dietary methyl donor supplementation hypermethylates the "Axin[Fu]" allele and thereby reduces incidence and/or severity of tail kinks in "Axin[Fu]/+" mice. Female C57BL6/J mice were assigned randomly to either NIH-31 control diet (24 litters) or NIH-31 supplemented (22 litters) with extra folic acid, vitamin B[12], betaine, and choline two weeks before mating with "Axin[Fu]/+" males and throughout pregnancy and lactation. At age 21 d, offspring were rated for tail phenotype and tissues collected. CpG methylation of the "Axin[Fu]" allele was measured by bisulfite sequencing. Only 40% of supplemented vs. 70% of control "Axin[Fu]/+" offspring had tail kinks (p=0.001). Hypermethylation of the "Axin[Fu]" locus in tail DNA of supplemented offspring (p=0.01) appeared to completely mediate the effect of supplementation on tail phenotype. Interestingly, however, there was no effect of supplementation on "Axin[Fu]" methylation in liver (p=0.53). Hence, like at "A[vy]", establishment of epigenotype at the "Axin[Fu]" metastable epiallele is influenced by maternal nutrition. However, such effects may be tissue-specific and occur at diverse developmental periods.