| First Author | Jiang M | Year | 1998 |
| Journal | Proc Natl Acad Sci U S A | Volume | 95 |
| Issue | 6 | Pages | 3269-74 |
| PubMed ID | 9501252 | Mgi Jnum | J:46898 |
| Mgi Id | MGI:1202208 | Doi | 10.1073/pnas.95.6.3269 |
| Citation | Jiang M, et al. (1998) Multiple neurological abnormalities in mice deficient in the G protein Go. Proc Natl Acad Sci U S A 95(6):3269-74 |
| abstractText | The G protein G(o) is highly expressed in neurons and mediates effects of a group of rhodopsin-like receptors that includes the opioid, alpha(2)-adrenergic, M2 muscarinic, and somatostatin receptors. In vitro, G(o) is also activated by growth cone-associated protein of M-r 43,000 (GAP43) and the Alzheimer amyloid precursor protein, but it is not known whether this occurs in intact cells. To learn about the roles that G(o) may play in intact cells and whole body homeostasis, we disrupted the gene encoding the alpha subunits of G(o) in embryonic stem cells and derived G(o)-deficient mice. Mice with a disrupted alpha(o) gene (alpha(o)(-/-) mice) lived but had an average half-life of only about 7 weeks. No G(o) alpha was detectable in homogenates of alpha(o)(-/-) mice by ADP- ribosylation with pertussis toxin, At the cellular level, inhibition of cardiac adenylyl cyclase by carbachol (50- 55% at saturation) was unaffected, but inhibition of Ca2+ channel currents by opioid receptor agonist in dorsal root ganglion cells was decreased by 30%, and in 25% of the alpha(o)(-/-) cells examined, the Ca2+ channel was activated at voltages that were 13.3 +/- 1.7 mV lower than in their counterparts, Loss of alpha(o) was not accompanied by appearance of significant amounts of active free beta gamma dimers (prepulse test), At the level of the living animal, G(o)-deficient mice are hyperalgesic (hot-plate test) and display a severe motor control impairment (falling from rotarods and 1-inch wide beams). In spite of this deficiency, alpha(o)(-/-) mice are hyperactive and exhibit a turning behavior that has them running in circles for hours on end, bath in cages and in open-field tests. Except for one, all alpha(o)(-/-) mice turned only counterclockwise. These findings indicate that G(o) plays a major role in motor control, in motor behavior, and in pain perception and also predict involvement of G(o) in Ca2+ channel regulation by an unknown mechanism. |
