Chen S C, Ehrhard P, Goldowitz D, Smeyne R J
Neurogenetics Program, Department of CNS Research, Hoffmann-LaRoche, Nutley, NJ 07110, USA.
Brain Res. 1997 Dec 19;778(2):251-64. doi: 10.1016/s0006-8993(97)00896-2.
G-protein-gated inward rectifying potassium channels (GIRKs) are a newly identified gene family. These gene products are thought to form functional channels through the assembly of heteromeric subunits. Recently, it has been demonstrated that a point mutation in the GIRK2 gene, one of the GIRK family members, is the cause of the neurological and reproductive defects observed in the weaver (wv) mutant mouse. The mechanism(s) by which a single amino acid substitution in GIRK2 protein leads to the severe phenotypes in the wv / wv mouse is not fully understood. However, it implicates the importance of GIRK channels in neuronal development. To characterize the mRNA expression patterns of GIRK1-3 during mouse brain development we have used in situ hybridization analyses. We found that the expression of all three genes showed developmental regulation. In most areas that showed expression, the levels of GIRK1-3 transcripts reached their peak at around postnatal day 10 (P10). In general, GIRK1 showed the least fluctuation in its levels of expression during development, while dynamic changes were found with the levels of GIRK2 and GIRK3 transcripts. GIRK3 becomes the predominant inward rectifying K+-channel in the brain at later postnatal ages. In the CNS regions affected in the wv / wv mouse, GIRK2 is the predominant inward rectifying channel that is expressed. This suggests that the presence of the other subtypes are able to compensate for the mutated GIRK2 channel in weaver neurons that survive.
G蛋白门控内向整流钾通道（GIRKs）是一个新发现的基因家族。这些基因产物被认为通过异源亚基的组装形成功能性通道。最近，已经证明GIRK家族成员之一的GIRK2基因中的一个点突变是在韦弗（wv）突变小鼠中观察到的神经和生殖缺陷的原因。GIRK2蛋白中的单个氨基酸取代导致wv / wv小鼠出现严重表型的机制尚未完全了解。然而，这暗示了GIRK通道在神经元发育中的重要性。为了表征GIRK1 - 3在小鼠脑发育过程中的mRNA表达模式，我们使用了原位杂交分析。我们发现所有三个基因的表达都显示出发育调控。在大多数显示表达的区域，GIRK1 - 3转录本的水平在出生后第10天（P10）左右达到峰值。一般来说，GIRK1在发育过程中的表达水平波动最小，而GIRK2和GIRK3转录本的水平则有动态变化。在出生后较晚的年龄段，GIRK3成为大脑中主要的内向整流钾通道。在wv / wv小鼠受影响的中枢神经系统区域，GIRK2是表达的主要内向整流通道。这表明其他亚型的存在能够补偿存活的韦弗神经元中突变的GIRK2通道。
