Embryonic cardiomyocyte hypoplasia and craniofacial defects in Gαq/Gα11-mutant mice

Heterotrimeric G proteins of the G(q) 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 G(q) class of G proteins plays a crucial role in cardiac growth and development.