Rassoulzadegan M, Grandjean V, Gounon P, Cuzin F
Inserm U636, Ligue Nationale Contre le Cancer, F-06108 Nice, France.
Biochem Soc Trans. 2007 Jun;35(Pt 3):623-5. doi: 10.1042/BST0350623.
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.
遗传表观遗传变异最初在植物中被广泛认识和研究，直到最近才在哺乳动物中被报道。我们现已确定Kit基因座是小鼠中第一个副突变基因的例子。从Kit(tm1Alf)(/+)杂合子出生的Kit(+/+)纯合子维持并将突变杂合子特有的白斑表型传递给它们的后代。我们观察到副突变（Kit*）雄性小鼠精子中存在异常数量的RNA，这使我们考虑RNA介导遗传的可能性。在单细胞胚胎中显微注射副突变雄性小鼠的精子RNA或Kit特异性微小RNA miR-221和-222后，表观遗传修饰的有效建立进一步支持了RNA的作用。在本文中，我们描述了Kit*副突变动物中与野生型基因组相关的表型。对于孟德尔分析无法完全解释的家族性疾病易感性情况，副突变可能被认为是表观遗传修饰的一种可能性。
