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

First Author  Rassoulzadegan M Year  2006
Journal  Nature Volume  441
Issue  7092 Pages  469-74
PubMed ID  16724059 Mgi Jnum  J:109086
Mgi Id  MGI:3625683 Doi  10.1038/nature04674
Citation  Rassoulzadegan M, et al. (2006) RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441(7092):469-74
abstractText  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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