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- Title
RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse.
- Authors
Rassoulzadegan, Minoo; Grandjean, Valérie; Gounon, Pierre; Vincent, Stéphane; Gillot, Isabelle; Cuzin, François
- Abstract
Paramutation is a heritable epigenetic modification induced in plants by cross-talk between allelic loci. Here we report a similar modification of the mouse Kit gene in the progeny of heterozygotes with the null mutant Kit(tm1Alf) (a lacZ insertion). In spite of a homozygous wild-type genotype, their offspring maintain, to a variable extent, the white spots characteristic of Kit mutant animals. Efficiently inherited from either male or female parents, the modified phenotype results from a decrease in Kit messenger RNA levels with the accumulation of non-polyadenylated RNA molecules of abnormal sizes. Sustained transcriptional activity at the postmeiotic stages--at which time the gene is normally silent--leads to the accumulation of RNA in spermatozoa. Microinjection into fertilized eggs either of total RNA from Kit(tm1Alf/+) heterozygotes or of Kit-specific microRNAs induced a heritable white tail phenotype. Our results identify an unexpected mode of epigenetic inheritance associated with the zygotic transfer of RNA molecules.
- Publication
Nature, 2006, Vol 441, Issue 7092, p469
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature04674