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Expression and Function of the Gene Encoding the Voltage-Dependent Calcium Channel β3-Subunit in the Mouse Placenta
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
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2007 (English)In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 28, no 5-6, 412-420 p.Article in journal (Refereed) Published
Abstract [en]

Voltage-dependent Ca(2+) channels (VDCC) exist in most excitable cells and their properly regulated activity is essential for critical biological processes as many of these are sensitive to cellular Ca(2+) ion concentration. The ancillary cytoplasmic Ca(2+) channel beta subunits (CACNB) modulate Ca(2+) channel function and are required to enhance the number of functional channels in the plasma membrane. There are four genes encoding CACNB subunits and the gene encoding CACNB3 is over expressed in hyperplastic placentas of mouse interspecies hybrids. To determine the role of CACNB3 in the mouse placenta, we performed an expression and function analysis. Our results show that Cacnb3 exhibits specific spatial and temporal expression in the mouse placenta. Deletion of Cacnb3 does not produce a strong placental phenotype, which may be due to expression of other CACNB subunit encoding genes; however, sporadic occurrence of a labyrinthine architecture phenotype, characterized by reduced density of fetal blood vessels and decrease in pericyte number, could be observed. Down-regulation of Cacnb3 expression did not rescue placental hyperplasia in a model of interspecies hybrid placentas, which indicates that up-regulation in the hyperplastic placentas is a downstream event.

Place, publisher, year, edition, pages
2007. Vol. 28, no 5-6, 412-420 p.
Keyword [en]
Cacnb3, Spongiotrophoblast, Mouse placenta, Hyperplasia
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-94490DOI: 10.1016/j.placenta.2006.05.007ISI: 000246449700007PubMedID: 16822546OAI: oai:DiVA.org:uu-94490DiVA: diva2:168356
Available from: 2006-05-08 Created: 2006-05-08 Last updated: 2011-02-01Bibliographically 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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 181
Keyword
Developmental biology, hybrid dysgenesis effects, placental hyperplasia, functional screening, giant cell, glycogen cell, Utvecklingsbiologi
Identifiers
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)
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Available from: 2006-05-08 Created: 2006-05-08 Last updated: 2009-04-05Bibliographically approved

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Singh, UmashankarHeuchel, RainerFundele, Reinald

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