Publication Date:
1996-06-28
Description:
Homozygous weaver mice are profoundly ataxic because of the loss of granule cell neurons during cerebellar development. This granule cell loss appears to be caused by a genetic defect in the pore region (Gly156--〉Ser) of the heterotrimeric guanine nucleotide-binding protein (G protein)-gated inwardly rectifying potassium (K+) channel subunit (GIRK2). A related subunit, GIRK1, associates with GIRK2 to constitute a neuronal G protein-gated inward rectifier K+ channel. The weaver allele of the GIRK2 subunit (wvGIRK2) caused loss of K+ selectivity when expressed either as wvGIRK2 homomultimers or as GIRK1-wvGIRK2 heteromultimers. The mutation also let to loss of sensitivity to G protein betagamma dimers. Expression of wvGIRK2 subunits let to increased cell death, presumably as a result of basal nonselective channel opening.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Navarro, B -- Kennedy, M E -- Velimirovic, B -- Bhat, D -- Peterson, A S -- Clapham, D E -- New York, N.Y. -- Science. 1996 Jun 28;272(5270):1950-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658170" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Antisense Elements (Genetics)
;
CHO Cells
;
Cell Death
;
Cell Line
;
Cerebellum/cytology/*metabolism
;
Cricetinae
;
G Protein-Coupled Inwardly-Rectifying Potassium Channels
;
GTP-Binding Proteins/*physiology
;
Membrane Potentials
;
Mice
;
Mice, Neurologic Mutants
;
Molecular Sequence Data
;
Neurons/cytology/metabolism
;
Oocytes/cytology
;
Patch-Clamp Techniques
;
Point Mutation
;
Potassium Channels/genetics/*metabolism
;
*Potassium Channels, Inwardly Rectifying
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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