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Expression and functional analysis of genes deregulated in mouse placental overgrowth models: Car2 and Ncam1

Singh, Umashankar; Sun, Tong; Shi, Wei; Schulz, Ralph; Nuber, Ulrike LU ; Varanou, Aikaterini; Hemberger, Myriam C; Elliott, Rosemary W; Ohta, Hiroshi and Wakayama, Teruhiko, et al. (2005) In Developmental Dynamics 234(4). p.1034-1045
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... (More)
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. (Less)
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publication status
published
subject
keywords
Car2, Ncam1, placental growth, functional redundancy
in
Developmental Dynamics
volume
234
issue
4
pages
1034 - 1045
publisher
John Wiley & Sons
external identifiers
  • pmid:16247769
  • scopus:28444447362
ISSN
1097-0177
DOI
10.1002/dvdy.20597
language
English
LU publication?
no
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a31d5282-2b43-4e34-9f66-807327c757d9 (old id 1134192)
date added to LUP
2008-06-18 11:45:05
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2017-01-01 04:40:24
@article{a31d5282-2b43-4e34-9f66-807327c757d9,
  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.},
  author       = {Singh, Umashankar and Sun, Tong and Shi, Wei and Schulz, Ralph and Nuber, Ulrike and Varanou, Aikaterini and Hemberger, Myriam C and Elliott, Rosemary W and Ohta, Hiroshi and Wakayama, Teruhiko and Fundele, Reinald},
  issn         = {1097-0177},
  keyword      = {Car2,Ncam1,placental growth,functional redundancy},
  language     = {eng},
  number       = {4},
  pages        = {1034--1045},
  publisher    = {John Wiley & Sons},
  series       = {Developmental Dynamics},
  title        = {Expression and functional analysis of genes deregulated in mouse placental overgrowth models: Car2 and Ncam1},
  url          = {http://dx.doi.org/10.1002/dvdy.20597},
  volume       = {234},
  year         = {2005},
}