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. 2006 May 25;441(7092):469-74.
doi: 10.1038/nature04674.

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

Minoo Rassoulzadegan  1 , Valérie Grandjean, Pierre Gounon, Stéphane Vincent, Isabelle Gillot, François Cuzin
Affiliations
Free article

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

Minoo Rassoulzadegan et al. Nature. .
Free article

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.

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Comment in

  • Genetics: what is a gene?
    Pearson H. Pearson H. Nature. 2006 May 25;441(7092):398-401. doi: 10.1038/441398a. Nature. 2006. PMID: 16724031 No abstract available.
  • Genetics: paramutable possibilities.
    Soloway PD. Soloway PD. Nature. 2006 May 25;441(7092):413-4. doi: 10.1038/441413a. Nature. 2006. PMID: 16724044 No abstract available.

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