GENOMIC IMPRINTING IN RUMINANTS - ALLELE-SPECIFIC GENE-EXPRESSION IN PARTHENOGENETIC SHEEP

Studies in the mouse have established that both parental genomes are e ssential for normal embryonic development. Parthenogenetic mouse embry os (which have two maternal genomes and no paternal genome), for examp le, are growth-retarded and die at early postimplantation stages. The distinct maternal and paternal contributions are mediated by genomic i mprinting, an epigenetic mechanism by which the expression of certain genes is dependent on whether they are inherited from mother or father . Although comparative studies have established that many imprinted mo use (and rat) genes are allele-specifically expressed in humans as wel l (and vice versa), so far imprinting studies have not been performed in other mammalian species. When considering evolutionary theories of genomic imprinting, it would be important to know how widely it is con served among placental mammals. We have investigated its conservation in a bovid ruminant, the domestic sheep, by comparing parthenogenetic and normal control embryos. Our study establishes that, Like in the mo use, parthenogenetic development in sheep is associated with growth-re tardation and does not proceed beyond early fetal stages. These develo pmental abnormalities are most likely caused by imprinted genes. We de monstrate that, indeed, like in mice and humans, the growth-related PE G1/MEST and Insulin-like Growth Factor 2 (IGF2) genes are expressed fr om the paternal chromosome in sheep. These observations suggest that g enomic imprinting is conserved in a third, evolutionarily rather diver ged group of placental mammals, the ruminants.