Slesinger P A, Patil N, Liao Y J, Jan Y N, Jan L Y, Cox D R
Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco 94143-0724, USA.
Neuron. 1996 Feb;16(2):321-31. doi: 10.1016/s0896-6273(00)80050-1.
The weaver mutation corresponds to a substitution of glycine to serine in the H5 region of a G protein-gated inwardly rectifying K+ channel gene (GIRK2). By studying mutant GIRK2 weaver homomultimeric channels and heteromultimeric channels comprised of GIRK2 weaver and GIRK1 in Xenopus oocytes, we found that GIRK2 weaver homomultimeric channels lose their selectivity for K+ ions, giving rise to inappropriate receptor-activated and basally active Na+ currents, whereas heteromultimers of GIRK2 weaver and GIRK1 appeared to have reduced current. Immunohistochemical localization indicates that GIRK2 and GIRK1 proteins are expressed in the cerebellar neurons of mice at postnatal day 4, at a time when these neurons normally undergo differentiation. Thus, the aberrant behavior of mutant GIRK2 weaver channels could affect the development of weaver mice in at least two distinct ways.
韦弗突变对应于G蛋白门控内向整流钾离子通道基因（GIRK2）的H5区域中甘氨酸被丝氨酸取代。通过在非洲爪蟾卵母细胞中研究突变型GIRK2韦弗同多聚体通道以及由GIRK2韦弗和GIRK1组成的异多聚体通道，我们发现GIRK2韦弗同多聚体通道失去了对钾离子的选择性，从而产生不适当的受体激活的和基础活性的钠离子电流，而GIRK2韦弗和GIRK1的异多聚体似乎电流减小。免疫组织化学定位表明，GIRK2和GIRK1蛋白在出生后第4天的小鼠小脑神经元中表达，此时这些神经元通常正在经历分化。因此，突变型GIRK2韦弗通道的异常行为可能至少以两种不同方式影响韦弗小鼠的发育。
