Carboxypeptidase E in the mouse placenta.
Carboxypeptidase E (CPE) has important functions in processing of endocrine pro-peptides, such as pro-insulin, pro-opiomelanocortin, or pro-gonadotropin-releasing hormone, as evidenced by the hyper-pro-insulinemia, obesity, and sterility of Cpe mutant mice. Down-regulation of Cpe in enlarged placentas of interspecific hybrid (interspecies hybrid placental dysplasia (IHPD)) and cloned mice suggested that reduced CPE enzyme and receptor activity could underlie abnormal placental phenotypes. In this study, we have explored the role of Cpe in murine placentation by determining its expression at various stages of gestation, and by phenotypic analysis of Cpe mutant placentas. Our results show that Cpe and Carboxypeptidase D (Cpd), another carboxypeptidase with a very similar function, are strictly co-localized in the mouse placenta from late mid-gestation to term. We also show that absence of CPE causes a sporadic but striking placental phenotype characterized by an increase in giant and glycogen cell numbers and giant cell hypertrophy. Microarray-based transcriptional profiling of Cpe mutant placentas identified only a very small number of genes with altered expression, including Dtprp, which belongs to the prolactin gene family. Concordant deregulation of Cpe and Cpd in abnormal placentas of interspecies hybrids before the onset of IHPD phenotype and recapitulation of some phenotypes of IHPD hyperplastic placentas in Cpe mutant placentas suggests that these two genes are causally involved in IHPD and may function as speciation genes in the genus Mus.
Singh
Umashankar
U
Department of Development and Genetics, Evolutionary Biology Center, Uppsala University, 75236 Uppsala, Sweden.
Yu
Yang
Y
Kalinina
Elena
E
Konno
Toshihiro
T
Sun
Tong
T
Ohta
Hiroshi
H
Wakayama
Teruhiko
T
Soares
Michael J
MJ
Hemberger
Myriam
M
Fundele
Reinald H
RH
D000818:Animals; D043423:Carboxypeptidase H / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018899:CpG Islands; D005260:Female; D020869:Gene Expression Profiling; D015726:Giant Cells / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010641:Phenotype; D010920:Placenta / Q000201:enzymology*; D010929:Placentation / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D011388:Prolactin / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism
C489796:Dtprp protein, mouse; D011506:Proteins; D011388:Prolactin; D043423:Carboxypeptidase H; C094315:metallocarboxypeptidase D