Fumitoshi Ishino
Gene Research Center; Tokyo Institute of Technology
Nuclear transfer experiment is a very good tool for examining epigenetic states of nuclear donor cells. Pronuclear transplantation experiment led to discovery of genomic imprinting in mammals by producing parthenogenetic and androgenetic embryos. Somatic cloning is another nuclear transplantation experiment involving a reprogramming step by which terminally differentiated epigenetic states in somatic cells are initialized. Parental imprinted memories are stably maintained in the somatic cell lineage, Therefore, it is very interesting to know whether genomic imprinting mechanism functions normally or it is reprogrammed or disturbed during this step, causing several abnormal phenotypes observed in the somatic cloned animals.
Contrary to the previous observation of ES cell-derived cloned mice, genomic imprinting memory was faithfully maintained in the mouse somatic clones produced from fresh or primary cultured cells (1). This means that somatic cloning is also a very useful method for analyzing genomic imprinting status of nuclear donor cells.
Then, we analyzed mouse clones from primordial germ cells (PGCs) to examine the process of erasure of genomic imprinting memory. We found several intermediate states in this process and a common default state between male and female germ lines in the clone embryos from day 11.5 and day 12.5-13.5 PGCs, respectively (2). Interestingly, day 12.5 PGC clones showed early embryonic lethality as previously reported in PGC embryos from later stage of male PGCs (3). These results suggest that the default state of genomic imprinting cannot support normal embryonic development, revisiting a crucial role of genomic imprinting in mammalian development (2,3).
References:
Inoue, K. et al. Science 295, 297, 2002.
Lee, J, et al. Development (in press).
Kato, Y. et al. Development 126, 1823, 1999.