The weaver mutation of GIRK2 results in a loss of inwardly rectifying K+ current in cerebellar granule cells.
The weaver mutation of GIRK2 results in a loss of inwardly rectifying K+ current in cerebellar granule cells.
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GIRK2 的 Weaver 突变导致小脑颗粒细胞内向整流 K 电流丧失。
DOI：
10.1073/pnas.93.20.11191
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发表时间：
1996
影响因子：
11.1
通讯作者：
Goldowitz,D
中科院分区：
文献类型：
--
作者：
Surmeier,DJ;Mermelstein,PG;Goldowitz,D
小鼠的韦弗突变导致严重的共济失调，这是由于小脑颗粒细胞和黑质多巴胺能神经元的变性。最近的遗传学研究表明，GIRK 2基因在织布工中发生了改变。该基因编码G蛋白激活的内向整流K+通道蛋白（8）。该突变导致通道的成孔H5区域中的单个氨基酸取代（甘氨酸->丝氨酸）。这种突变的功能后果似乎取决于其他GIRK亚基的共表达-导致功能的获得或丧失。在这里，我们表明，G蛋白激活的内向整流K+电流显着减少携带突变等位基因的动物小脑颗粒细胞。这种减少在纯合神经元中最为明显。这些发现表明，韦弗神经元的死亡是由于GIRK 2介导的电流的损失，而不是非特异性阳离子电流的表达。
The weaver mutation in mice results in a severe ataxia that is attributable to the degeneration of cerebellar granule cells and dopaminergic neurons in the substantia nigra. Recent genetic studies indicate that the GIRK2 gene is altered in weaver. This gene codes for a G-protein-activated, inwardly rectifying K+ channel protein (8). The mutation results in a single amino acid substitution (glycine-->serine) in the pore-forming H5 region of the channel. The functional consequences of this mutation appear to depend upon the co-expression of other GIRK subunits--leading to either a gain or loss of function. Here, we show that G-protein-activated inwardly rectifying K+ currents are significantly reduced in cerebellar granule cells from animals carrying the mutant allele. The reduction is most pronounced in homozygous neurons. These findings suggest that the death of neurons in weaver is attributable to the loss of GIRK2-mediated currents, not to the expression of a nonspecific cation current.
影响因子：
3.4
作者：
HEGINBOTHAM, L;LU, Z;MACKINNON, R
通讯作者：
MACKINNON, R
胚胎施用丙硫氧嘧啶（PTU）后野生型和织布小脑的产后发育。
DOI：
10.1016/0165-3806(90)90151-n
发表时间：
1990
期刊：
Brain research. Developmental brain research
影响因子：
--
作者：
Smeyne,RJ;Goldowitz,D
通讯作者：
Goldowitz,D
DOI：
10.1006/bbrc.1995.2019
发表时间：
1995-07-17
影响因子：
3.1
作者：
DUPRAT, F;LESAGE, F;BARHANIN, J
通讯作者：
BARHANIN, J