Embryonic cardiomyocyte hypoplasia and craniofacial defects in G alpha q/G alpha 11-mutant mice.
Heterotrimeric G proteins of the Gq class have been implicated in signaling pathways regulating cardiac growth under physiological and pathological conditions. Knockout mice carrying inactivating mutations in both of the widely expressed G alpha q class genes, G alpha q and G alpha 11, demonstrate that at least two active alleles of these genes are required for extrauterine life. Mice carrying only one intact allele [G alpha q(-/+);G alpha 11(-/-) or G alpha q(-/-);G alpha 11(-/+)] died shortly after birth. These mutants showed a high incidence of cardiac malformation. In addition, G alpha q(-/-);G alpha 11(-/+) newborns suffered from craniofacial defects. Mice lacking both G alpha q and G alpha 11 [G alpha q(-/-);G alpha 11(-/-)] died at embryonic day 11 due to cardiomyocyte hypoplasia. These data demonstrate overlap in G alpha q and G alpha 11 gene functions and indicate that the Gq class of G proteins plays a crucial role in cardiac growth and development.
Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany. stoff@zedat.fu-berlin.de
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Offermanns
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Zhao
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Gohla
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Sarosi
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Simon
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Wilkie
D000483:Alleles; D000818:Animals; D000831:Animals, Newborn / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000196:embryology* / Q000235:genetics* / Q000473:pathology; D003433:Crosses, Genetic; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D018628:Gene Dosage; D006330:Heart Defects, Congenital / Q000196:embryology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology*
D019204:GTP-Binding Proteins