A G184S point mutation was created in the Gnai2 (guanine nucleotide binding protein (G protein), alpha inhibiting 2; also called Gαi2) gene which disrupts interactions with regulator of G protein signaling (RGS) proteins that normally deactivate Gα G protein signals. A complex phenotype affecting multiple organ systems (heart, myeloid, skeletal, and central nervous system) can be observed. Homozygous mice and their cardiocytes exhibit enhanced muscarinic (M2) but not adenosine (A1) receptor-mediated responses. Isoproterenol-stimulated beating rates of heterozygous and homozygous hearts are significantly more sensitive to inhibition to carbachol than are those of wildtype mice.
Homozygous mice show slightly reduced adiposity. Unlike females, males placed on a high-fat diet are resistant to weight gain and have decreased body fat as compared to wildtype mice. Both males and females exhibit enhanced insulin sensitivity (protected from insulin resistance) and increased glucose tolerance.
Although fertile, both homozygotes and heterozygotes demonstrate reduced viability and decreased body weight. Homozygotes are born in low numbers for unknown reasons. Shortened long bones, growth retardation, enlarged spleen, elevated neutrophil and monocyte counts, enlarged heart, and behavioral hyperactivity are also observed primarily in homozygotes. This strain may be useful in studies of signal transduction, pharmacology, diabetes, epilepsy, thrombosis, cardiology, and developmental biology.
