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Expression and Functional Analysis of Fibulin-1 (Fbln1) During Normal and Abnormal Placental Development of the Mouse
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 Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
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2006 (English)In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 27, no 9-10, 1014-1021 p.Article in journal (Refereed) Published
Abstract [en]

The extracellular matrix protein fibulin-1 (FBLN1) is an important component of blood vessel walls, as shown by the lethality of mice with homozygous targeted deletion of the Fbln1 gene. Here, we show that a murine placental overgrowth phenotype is associated with elevated Fbln1 transcript levels, suggesting that the gene and its product have a functional role in placentation. Fbln1 exhibits a specific expression pattern in the mouse placenta. Transcripts could not be detected prior to day 12. In subsequent stages, Fbln1 was expressed strongly in the spongiotrophoblast. Other sites of expression were endothelia of large fetal blood vessels, a tissue type reported to not express this gene. In addition, a subset of giant cells expressed the gene. This giant cell specific expression was strongly increased in hyperplastic placentas. Analysis of the placentation in fibulin null mice did not show any abnormality. Attempts to rescue the placental phenotypes of a congenic model of interspecies hybrid placental dysplasia (IHPD) by normalizing expression of Fbln1 proved that Fbln1 alone is not the key cause of phenotypes in these models of placental hyperplasia.

Place, publisher, year, edition, pages
2006. Vol. 27, no 9-10, 1014-1021 p.
Keyword [en]
Fibulin-1, Hyperplasia, Mouse placenta, Spongiotrophoblast
National Category
Developmental Biology
Identifiers
URN: urn:nbn:se:uu:diva-94489DOI: 10.1016/j.placenta.2005.10.009ISI: 000240312200011PubMedID: 16338003OAI: oai:DiVA.org:uu-94489DiVA: diva2:168355
Available from: 2006-05-08 Created: 2006-05-08 Last updated: 2011-02-23Bibliographically 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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Fundele, Reinald

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