RNA-mediated non-Mendelian inheritance of an epigenetic change in the mouse. Researchers identified a novel form of epigenetic inheritance in mice, where an epigenetic modification in the Kit gene is passed from parents to offspring through RNA molecules, rather than through traditional Mendelian inheritance. This phenomenon, termed paramutation, was observed in the progeny of heterozygous mice carrying a null mutant allele of the Kit gene. Despite having a wild-type genotype, these offspring exhibited a white-spotted phenotype characteristic of Kit mutants. The modified phenotype was inherited efficiently from both male and female parents and was associated with reduced levels of Kit mRNA and the accumulation of non-polyadenylated RNA molecules of abnormal sizes. The study also showed that microinjection of total RNA from heterozygous Kit mice or specific microRNAs into fertilized eggs could induce a heritable white tail phenotype. These findings suggest that RNA molecules can be transferred to the zygote and contribute to epigenetic inheritance. The study also revealed that RNA molecules were present in the sperm of Kit heterozygotes and that these RNA molecules could be responsible for the paramutated phenotype. The research highlights the potential role of RNA in epigenetic inheritance and provides new insights into the mechanisms of non-Mendelian inheritance in animals. The study was conducted in mice and provides a model for understanding the role of RNA in epigenetic inheritance. The findings have implications for understanding the mechanisms of epigenetic inheritance in animals and may have applications in the development of new therapeutic strategies for genetic disorders.RNA-mediated non-Mendelian inheritance of an epigenetic change in the mouse. Researchers identified a novel form of epigenetic inheritance in mice, where an epigenetic modification in the Kit gene is passed from parents to offspring through RNA molecules, rather than through traditional Mendelian inheritance. This phenomenon, termed paramutation, was observed in the progeny of heterozygous mice carrying a null mutant allele of the Kit gene. Despite having a wild-type genotype, these offspring exhibited a white-spotted phenotype characteristic of Kit mutants. The modified phenotype was inherited efficiently from both male and female parents and was associated with reduced levels of Kit mRNA and the accumulation of non-polyadenylated RNA molecules of abnormal sizes. The study also showed that microinjection of total RNA from heterozygous Kit mice or specific microRNAs into fertilized eggs could induce a heritable white tail phenotype. These findings suggest that RNA molecules can be transferred to the zygote and contribute to epigenetic inheritance. The study also revealed that RNA molecules were present in the sperm of Kit heterozygotes and that these RNA molecules could be responsible for the paramutated phenotype. The research highlights the potential role of RNA in epigenetic inheritance and provides new insights into the mechanisms of non-Mendelian inheritance in animals. The study was conducted in mice and provides a model for understanding the role of RNA in epigenetic inheritance. The findings have implications for understanding the mechanisms of epigenetic inheritance in animals and may have applications in the development of new therapeutic strategies for genetic disorders.