Epigenetic regulation in mammalian development and dysfunction: the effects of somatic cloning and genomic imprinting

Abstract

Although somatic cell cloning has been accomplished in several mammalian species, its efficiency remains considerably low due to fetal mortality during the pre- and perinatal periods, which suggests incomplete initialization of epigenetic memories during the somatic cloning procedure. Genomic imprinting is an epigenetic mechanism that produces functional differences between the paternal and maternal genomes, and plays an essential role in mammalian development and growth. Therefore, it is very important to examine the genomic imprinting status of somatic clones. The placenta is one of the most commonly affected organs in the somatic clones. We confirmed that parental-origin-specific monoallelic expression of imprinted genes was maintained faithfully in cloned embryos and abnormal placentas. However, reduced expression was observed for several genes, including certain imprinted genes in both day 12.5 and term placentas. These results suggest that the development process in cloned mice is not identical to that in normal mice. We analyzed mouse clone embryos, which were produced from primordial germ cells (PGCs), and characterized the initialization of the parental imprinted memories. Memory erasure proceeded in a step-wise manner and was coordinated specifically for each imprinted gene at embryonic day 11.5, followed by the establishment of default imprinting states that were common to both male and female germ lines.