title: Disruption of G-protein γ5 subtype causes embryonic lethality in mice.
abstract: 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 αsubtypes, there is growing recognition that similarly divergent βγ dimers also regulate these processes. In this paper, we show that targeted disruption of the mouse Gng5 gene encoding the γ5 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 γ subunits in directing the assembly of functionally distinct G-αβγ trimers that are responsible for regulating diverse biological processes. Specifically, the finding that loss of the G-γ5 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-βγ5 dependent signaling contributes to the pathogenesis of human congenital heart problems.
authors.affiliation: The Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, United States of America.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Moon
authors.affiliation: The Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, United States of America.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Stauffer
authors.affiliation: The Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, United States of America.
authors.forename: William F
authors.initials: WF
authors.lastname: Schwindinger
authors.affiliation: The Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, United States of America.
authors.forename: Kathy
authors.initials: K
authors.lastname: Sheridan
authors.affiliation: The Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, United States of America.
authors.forename: Ashley
authors.initials: A
authors.lastname: Firment
authors.affiliation: The Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, United States of America.
authors.forename: Janet D
authors.initials: JD
authors.lastname: Robishaw
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001934:Branchial Region / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D049109:Cell Proliferation; D003433:Crosses, Genetic; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D056426:Genetic Loci / Q000235:genetics; D005838:Genotype; D006352:Heart Ventricles / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D044388:GTP-Binding Protein gamma Subunits; C000592773:Gng5 protein, mouse