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. |