Navarro B, Kennedy M E, Velimirovíc B, Bhat D, Peterson A S, Clapham D E
Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Science. 1996 Jun 28;272(5270):1950-3. doi: 10.1126/science.272.5270.1950.
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.
纯合的韦弗氏小鼠由于小脑发育过程中颗粒细胞神经元的丧失而严重共济失调。这种颗粒细胞的丧失似乎是由异三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）门控内向整流钾（K+）通道亚基（GIRK2）孔区的基因缺陷（Gly156→Ser）引起的。一个相关亚基GIRK1与GIRK2结合，构成神经元G蛋白门控内向整流K+通道。GIRK2亚基的韦弗氏等位基因（wvGIRK2）无论是作为wvGIRK2同多聚体还是作为GIRK1-wvGIRK2异多聚体表达时，都会导致K+选择性丧失。该突变还导致对G蛋白βγ二聚体的敏感性丧失。wvGIRK2亚基的表达导致细胞死亡增加，这可能是由于基础非选择性通道开放所致。
