2 CDC25 HOMOLOGS ARE DIFFERENTIALLY EXPRESSED DURING MOUSE DEVELOPMENT

The cdc25 gene product is a tyrosine phosphatase that acts as an initi ator of M-phase in eukaryotic cell cycles by activating p34(cdc2). Her e we describe the cloning and characterization of the developmental ex pression pattern of two mouse cnc25 homologs, Sequence comparison of t he mouse genes with human CDC25 genes reveal that they are most likely the mouse homologs of human CDC25A and CDC25B respectively, Mouse cdc 25a, which has not been described previously, shares 84% sequence iden tity with human CDC25A and has a highly conserved phosphatase domain c haracteristic of all cdc25 genes, A glutathione-s-transferase-cdc25a f usion protein can hydrolyze para-nitrophenylphosphate confirming that cdc25a is a phosphatase. In adult mice, cdc25a transcripts are express ed at high levels in the testis and at lower levels in the ovary, part icularly in germ cells; a pattern similar to that of twn, a Drosophila homolog of cdc25. Lower levels of transcript are also observed in kid ney, liver, heart and muscle, a transcription pattern that partially o verlaps, but is distinct from that of cdc25b. Similarly, in the postim plantation embryo cdc25a transcripts are expressed in a pattern that d iffers from that of cdc25b, cdc25a expression is observed in most deve loping embryonic organs while cdc25b expression is more restricted, An extended analysis of cdc25a and cdc25b expression in preimplantation embryos has also been carried out, These studies reveal that cdc25b tr anscripts are expressed in the one-cell embryo, decline at the two-cel l stage and are re-expressed at the four-cell stage, following the swi tch from maternal to zygotic transcription which mirrors the expressio n of string, another Drosophila homolog of cdc25, In comparison, cdc25 a is not expressed in the preimplantation embryo until the late blasto cyst stage of development, correlating with the establishment of a mor e typical G(1) phase in the embryonic cell cycles. Both cdc25a and cdc 25b transcripts are expressed at high levels in the inner cell mass an d the trophectoderm, which proliferate rapidly prior to implantation. These data suggest the cdc25 genes may have distinct roles in regulati ng the pattern of cell division during mouse embryogenesis and gametog enesis.