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. |