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Different Molecular Mechanisms Underlie Placental Overgrowth Phenotypes Caused by Interspecies Hybridization, Cloning, and Esx1 Mutation
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
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2004 (English)In: Developmental Dynamics, ISSN 1058-8388, Vol. 230, no 1, 149-164 p.Article in journal (Refereed) Published
Abstract [en]

To obtain a deeper insight into the genes and gene networks involved in the development of placentopathies, we have assessed global gene expression in three different models of placental hyperplasia caused by interspecies hybridization (IHPD), cloning by nuclear transfer, and mutation of the Esx1 gene, respectively. Comparison of gene expression profiles of approximately 13,000 expressed sequence tags (ESTs) identified specific subsets of genes with changed expression levels in IHPD, cloned, and Esx1 mutant placentas. Of interest, only one gene of known function and one EST of unknown function were found common to all three placentopathies; however, a significant number of ESTs were common to IHPD and cloned placentas. In contrast, only one gene was shared between IHPD and Esx1 mutant, and cloned and Esx1 mutant placentas, respectively. These genes common to different abnormal placental growth genotypes are likely to be important in the occurrence of placentopathy.

Place, publisher, year, edition, pages
2004. Vol. 230, no 1, 149-164 p.
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-94487DOI: 10.1002/dvdy.20024PubMedID: 15108320OAI: oai:DiVA.org:uu-94487DiVA: diva2:168353
IHPD, clones, Esx1, placental hyperplasia, global gene expression
Available from: 2006-05-08 Created: 2006-05-08 Last updated: 2010-02-05Bibliographically approved
In thesis
1. New Functions for Old Genes in the Mouse Placenta
Open this publication in new window or tab >>New Functions for Old Genes in the Mouse Placenta
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Different species are separated by pre-zygotic reproductive barriers which impede gene flow between them. Rarely, when pre-zygotic barriers break down, interspecific hybrids are produced that display abnormal phenotypes, collectively called hybrid dysgenesis effects. Interspecies hybrid placental dysplasia (IHPD) in the genus Mus is a very consistent X-linked hybrid dysgenesis effect. Reproductive cloning and mutation of the gene Esx1 lead to placental hyperplasias with phenotypic similarities to IHPD. Comparative gene expression analysis of these three different models of placental hyperplasia showed that different mechanisms underlie these placental hyperplasias. We also identified several genes for which roles in placentation had not been studied earlier. We screened five of these genes, Car2, Ncam1, Fbln1, Cacnb3 and Cpe for their functions in placentation. Analysis of the spatio-temporal expression patterns of these genes during mouse placental development showed that they are ectopically expressed in IHPD placentas. Placental phenotype and gene expression was then studied in mice mutant for these genes. Our results show that complicated by the expression of functional counterparts, deletion of these genes failed to produce any consistent phenotype. Incompletely penetrant phenotypes were found in Cacnb3 and Cpe mutants. The Cpe mutant placentas recapitulated some IHPD phenotypes, despite co-expression of Cpd, a functionally redundant gene. Deregulated expression of Cpe and Cpd prior to manifestation of IHPD phenotype indicated that these are causally involved in IHPD and might be speciation genes in the genus Mus. We found that AT24 placentas also exhibit deregulated expression of these genes and could be used as a model to study IHPD. We tried rescuing the AT24 placental phenotype, by decreasing the expression of the over expressed genes. Normalization of transcript levels of these genes did not rescue the AT24 phenotype, thus indicating that up-regulation of these genes is a down-stream event in the generation of IHPD.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 53 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 181
Developmental biology, hybrid dysgenesis effects, placental hyperplasia, functional screening, giant cell, glycogen cell, Utvecklingsbiologi
urn:nbn:se:uu:diva-6882 (URN)91-554-6566-8 (ISBN)
Public defence
2006-05-30, Lindahlsalen, EBC, Norbyvägen 18A, Uppsala, 10:00 (English)
Available from: 2006-05-08 Created: 2006-05-08 Last updated: 2009-04-05Bibliographically approved

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