title: Expression and functional analysis of genes deregulated in mouse placental overgrowth models: Car2 and Ncam1.
abstract: Different causes, such as maternal diabetes, cloning by nuclear transfer, interspecific hybridization, and deletion of some genes such as Esx1, Ipl, or Cdkn1c, may underlie placental overgrowth. In a previous study, we carried out comparative gene expression analysis in three models of placental hyperplasias, cloning, interspecies hybridization (IHPD), and Esx1 deletion. This study identified a large number of genes that exhibited differential expression between normal and enlarged placentas; however, it remained unclear how altered expression of any specific gene was related to any specific placental phenotype. In the present study, we focused on two genes, Car2 and Ncam1, which both exhibited increased expression in interspecies and cloned hyperplastic placentas. Apart from a detailed expression analysis of both genes during normal murine placentation, we also assessed morphology of placentas that were null for Car2 or Ncam1. Finally, we attempted to rescue placental hyperplasia in a congenic model of IHPD by decreasing transcript levels of Car2 or Ncam1. In situ analysis showed that both genes are expressed mainly in the spongiotrophoblast, however, expression patterns exhibited significant variability during development. Contrary to expectations, homozygous deletion of either Car2 or Ncam1 did not result in placental phenotypes. However, expression analysis of Car3 and Ncam2, which can take over the function of Car2 and Ncam1, respectively, indicated a possible rescue mechanism, as Car3 and Ncam2 were expressed in spongiotrophoblast of Car2 and Ncam1 mutant placentas. On the other hand, downregulation of either Car2 or Ncam1 did not rescue any of the placental phenotypes of AT24 placentas, a congenic model for interspecies hybrid placentas. This strongly suggested that altered expression of Car2 and Ncam1 is a downstream event in placental hyperplasia.
authors.affiliation: Department of Development and Genetics, Evolutionary Biology Center, Uppsala University, Sweden.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Singh
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Ralph
authors.initials: R
authors.lastname: Schulz
authors.forename: Ulrike A
authors.initials: UA
authors.lastname: Nuber
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Varanou
authors.forename: Myriam C
authors.initials: MC
authors.lastname: Hemberger
authors.forename: Rosemary W
authors.initials: RW
authors.lastname: Elliott
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohta
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Wakayama
authors.forename: Reinald
authors.initials: R
authors.lastname: Fundele
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism*; D024402:Carbonic Anhydrase II / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010922:Placenta Diseases / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D019002:CD56 Antigen; D017931:DNA Primers; C501063:Ncam1 protein, mouse; D024402:Carbonic Anhydrase II