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Publication : Essential role for Galpha13 in endothelial cells during embryonic development.

First Author  Ruppel KM Year  2005
Journal  Proc Natl Acad Sci U S A Volume  102
Issue  23 Pages  8281-6
PubMed ID  15919816 Mgi Jnum  J:99731
Mgi Id  MGI:3583513 Doi  10.1073/pnas.0503326102
Citation  Ruppel KM, et al. (2005) Essential role for Galpha13 in endothelial cells during embryonic development. Proc Natl Acad Sci U S A 102(23):8281-6
abstractText  Toward identifying the roles of protease-activated receptor-1 (PAR1) and other G protein-coupled receptors important for vascular development, we investigated the role of Galpha13 in endothelial cells in the mouse embryo. LacZ inserted into Galpha13 exon 1 was highly expressed in endothelial cells at midgestation. Endothelial-specific Galpha13 knockout embryos died at embryonic days 9.5-11.5 and resembled the PAR1 knockout. Restoration of Galpha13 expression in endothelial cells by use of a Tie2 promoter-driven Galpha13 transgene rescued development of endothelial-specific Galpha13 knockout embryos as well the embryonic day 9.5 vascular phenotype in Galpha13 conventional knockouts; transgene-positive Galpha13-/- embryos developed for several days beyond their transgene-negative Galpha13-/- littermates and then manifested a previously uncharacterized phenotype that included intracranial bleeding and exencephaly. Taken together, our results suggest a critical role for Galpha13 in endothelial cells during vascular development, place Galpha13 as a candidate mediator of PAR1 signaling in this process, and reveal roles for Galpha13 in other cell types in the mammalian embryo.
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