Disruption of G-Protein [gamma].sub.5 Subtype Causes Embryonic Lethality in Mice

Heterotrimeric G-proteins modulate many processes essential for embryonic development including cellular proliferation, migration, differentiation, and survival. Although most research has focused on identifying the roles of the various [alpha]subtypes, there is growing recognition that similarly divergent [beta][gamma] dimers also regulate these processes. In this paper, we show that targeted disruption of the mouse Gng5 gene encoding the [gamma].sub.5 subtype produces embryonic lethality associated with severe head and heart defects. Collectively, these results add to a growing body of data that identify critical roles for the [gamma] subunits in directing the assembly of functionally distinct G-[alpha][beta][gamma] trimers that are responsible for regulating diverse biological processes. Specifically, the finding that loss of the G-[gamma].sub.5 subtype is associated with a reduced number of cardiac precursor cells not only provides a causal basis for the mouse phenotype but also raises the possibility that G-[beta][gamma].sub.5 dependent signaling contributes to the pathogenesis of human congenital heart problems.