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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
Affiliation:
AA(Inserm, U636, F-06108 Nice, France), AB(Inserm, U636, F-06108 Nice, France), AC(Centre Commun de Microscopie Appliquée, Université de Nice-Sophia Antipolis, F-06108 Nice, France), AD(Inserm, U636, F-06108 Nice, France), AE(Inserm, U636, F-06108 Nice, France), AF(Inserm, U636, F-06108 Nice, France)
Publication:
Nature, Volume 441, Issue 7092, pp. 469-474 (2006). (Nature Homepage)
Publication Date:
05/2006
Origin:
NATURE
Abstract Copyright:
(c) 2006: Nature
DOI:
10.1038/nature04674
Bibliographic Code:
2006Natur.441..469R

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 Kittm1Alf (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 Kittm1Alf/+ 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.
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