Multiple neurological abnormalities in mice deficient in the G protein G o

• DOI: 10.1073/pnas.95.6.3269
• Publication Date: 2002-07-26T14:42:40Z
• Authors: Meisheng Jiang; Michael S. Gold; Guylain Boulay; Karsten Spicher; Michael Peyton; Philippe Brabet; Yogambul Srinivasan; Uwe Rudolph; Gaylord Ellison; Lutz Birnbaumer
• Keywords: Neurons; 0301 basic medicine; Behavior, Animal; Myocardium; Electric Conductivity; GTP-Binding Protein alpha Subunits, Gi-Go; Motor Activity; Nervous System Malformations; Mice, Mutant Strains; 3. Good health; Mice; 03 medical and health sciences; GTP-Binding Proteins; Hyperalgesia; Ganglia, Spinal; Animals; Abnormalities, Multiple; Calcium; Dimerization; Adenylyl Cyclases

The G protein o is highly expressed in neurons and mediates effects of a group rhodopsin-like receptors that includes the opioid, α 2 -adrenergic, M2 muscarinic, somatostatin receptors. In vitro , also activated by growth cone-associated M r 43,000 (GAP43) Alzheimer amyloid precursor protein, but it not known whether this occurs intact cells. To learn about roles may play cells whole body homeostasis, we disrupted gene encoding subunits embryonic stem derived -deficient mice. Mice with (α −/− mice) lived had an average half-life only 7 weeks. No was detectable homogenates mice ADP-ribosylation pertussis toxin. At cellular level, inhibition cardiac adenylyl cyclase carbachol (50–55% at saturation) unaffected, Ca 2+ channel currents opioid receptor agonist dorsal root ganglion decreased 30%, 25% examined, voltages were 13.3 ± 1.7 mV lower than their counterparts. Loss accompanied appearance significant amounts active free βγ dimers (prepulse test). level living animal, are hyperalgesic (hot-plate test) display severe motor control impairment (falling from rotarods 1-inch wide beams). spite deficiency, hyperactive exhibit turning behavior has them running circles for hours on end, both cages open-field tests. Except one, all turned counterclockwise. These findings indicate plays major role control, behavior, pain perception predict involvement regulation unknown mechanism.