Cell death in weaver mouse cerebellum.
Mice with the weaver mutation exhibit an uneven weave to their gait, ataxia, mild locomotor hyperactivity and, occasionally, tonic-clonic seizures. A single amino acid mutation in a G-protein coupled, inwardly rectifying K+ channel, GIRK2, gives rise to the symptoms seen in the weaver mice. Two areas of the brain are primarily affected. Cerebellar granule cell neurons die soon after birth and dopaminergic neurons are severely depleted in the substantia nigra. In this article we review recent studies of wild-type and mutant GIRK channels found in native cells or introduced into expression systems. We also review two models that explain some of the details leading to the neuronal cell death observed in weaver mice.
Harkins
Amy B
AB
Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois 60637, USA. amy@drugs.bsd.uchicago.edu
Fox
Aaron P
AP
D000818:Animals; D016923:Cell Death / Q000235:genetics; D002526:Cerebellar Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics*; D008959:Models, Neurological; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000172:deficiency* / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying