Maternal Ethanol Consumption Alters the Epigenotype and the Phenotype of Offspring in a Mouse Model 英文参考文献.docVIP

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Maternal Ethanol Consumption Alters the Epigenotype and the Phenotype of Offspring in a Mouse Model 英文参考文献.doc

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Maternal Ethanol Consumption Alters the Epigenotype and the Phenotype of Offspring in a Mouse Model 英文参考文献

MaternalEthanolConsumptionAlterstheEpigenotype andthePhenotypeofOffspringinaMouseModel NinaKaminen-Ahola1,ArttuAhola1,2,MuratMaga3,Kylie-AnnMallitt1,PaulFahey1,TimothyC.Cox3, EmmaWhitelaw1,4,SuyinnChong1,4 * 1Division of Genetics and Population Health, Queensland Institute of Medical Research, Herston, Australia, 2Department of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland, 3Division of Craniofacial Medicine, Department of Pediatrics,University of Washington, Seattle, Washington, United States of America,4GriffithMedicalResearchCollege,GriffithUniversityandtheQueenslandInstituteofMedicalResearch,Herston,Australia Abstract Recentstudieshaveshownthatexposuretosomenutritionalsupplementsandchemicalsinuterocanaffecttheepigenome of the developing mouse embryo, resulting in adult disease. Our hypothesis is that epigenetics is also involved in the gestationalprogrammingofadultphenotypebyalcohol.Wehavedevelopedamodelofgestationalethanolexposurein themousebasedonmaternaladlibitum ingestionof10%(v/v)ethanolbetweengestationaldays0.5–8.5andobserved changes in the expression of an epigenetically-sensitive allele, Agouti viable yellow (Avy), in the offspring. We found that exposuretoethanolincreasestheprobabilityoftranscriptionalsilencingatthislocus,resultinginmoremicewithanagouti- coloredcoat.Asexpected,transcriptionalsilencingcorrelatedwithhypermethylationatAvy.Thisdemonstrates,forthefirst time, that ethanol can affect adult phenotype by altering the epigenotype of the early embryo. Interestingly, we also detectedpostnatalgrowthrestrictionandcraniofacialdysmorphologyreminiscentoffetalalcoholsyndrome,incongenica/ asiblingsoftheAvymice.Thesefindingssuggestthatmoderateethanolexposureinuteroiscapableofinducingchangesin theexpressionofgenesotherthanAvy,aconclusionsupportedbyourgenome-wideanalysisofgeneexpressioninthese mice.Inaddition,offspringoffemalemicegivenfreeaccessto10%(v/v)ethanolforfourdaysperweekfortenweeksprior toconceptionalsoshowedi