title: Inheritance of an epigenetic change in the mouse: a new role for RNA.
abstract: Hereditary epigenetic variation, initially recognized and studied extensively in plants, had not been reported in mammals until recently. We have now identified the Kit locus as the first example of a paramutable gene of the mouse. Kit(+/+) homozygotes born from Kit(tm1Alf)(/+) heterozygotes maintain and transmit to their progeny the white-spotted phenotype characteristic of the mutant heterozygote. Our observation of unusual amounts of RNA in the sperm of the paramutated (Kit*) males had led us to consider the possibility of RNA-mediated inheritance. A role for RNA was supported further by the efficient establishment of the epigenetic modification following microinjection in one-cell embryos of either sperm RNA of the paramutated males or of the Kit-specific microRNAs miR-221 and -222. In this article, we describe the phenotypes associated with the wild-type genome in the Kit* paramutated animals. Paramutation may be considered to be one possibility of epigenetic modification in the case of familial disease predispositions that are not fully accounted for by Mendelian analysis.
authors.affiliation: Inserm U636, Ligue Nationale Contre le Cancer, F-06108 Nice, France. minoo@unice.fr
authors.forename: M
authors.initials: M
authors.lastname: Rassoulzadegan
authors.forename: V
authors.initials: V
authors.lastname: Grandjean
authors.forename: P
authors.initials: P
authors.lastname: Gounon
authors.forename: F
authors.initials: F
authors.lastname: Cuzin
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D010641:Phenotype; D011247:Pregnancy; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012880:Skin Pigmentation / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D019009:Proto-Oncogene Proteins c-kit