RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse

Minoo Rassoulzadegan (), Valérie Grandjean, Pierre Gounon, Stéphane Vincent, Isabelle Gillot and François Cuzin
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Minoo Rassoulzadegan: Inserm, U636
Valérie Grandjean: Inserm, U636
Pierre Gounon: Centre Commun de Microscopie Appliquée, Université de Nice-Sophia Antipolis
Stéphane Vincent: Inserm, U636
Isabelle Gillot: Inserm, U636
François Cuzin: Inserm, U636

Nature, 2006, vol. 441, issue 7092, 469-474

Abstract: 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.

Date: 2006
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DOI: 10.1038/nature04674

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