RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse.
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.
Rassoulzadegan
Minoo
M
Inserm, U636, F-06108 Nice, France. minoo@unice.fr
Grandjean
Valérie
V
Gounon
Pierre
P
Vincent
Stéphane
S
Gillot
Isabelle
I
Cuzin
François
F
D000483:Alleles; D000818:Animals; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005838:Genotype; D040941:Heredity / Q000235:genetics*; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012313:RNA / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism
D012333:RNA, Messenger; D012313:RNA; D019009:Proto-Oncogene Proteins c-kit