Cox G A, Lutz C M, Yang C L, Biemesderfer D, Bronson R T, Fu A, Aronson P S, Noebels J L, Frankel W N
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Cell. 1997 Oct 3;91(1):139-48. doi: 10.1016/s0092-8674(01)80016-7.
The "housekeeping" sodium/hydrogen exchanger, NHE1, mediates the electroneutral 1:1 exchange of Na+ and H+ across the plasma membrane. NHE1 is ubiquitous and is studied extensively for regulation of pHi, cell volume, and response to growth factors. We describe a spontaneous mouse mutant, slow-wave epilepsy, (swe), with a neurological syndrome including ataxia and a unique epilepsy phenotype consisting of 3/sec absence and tonic-clonic seizures. swe was fine-mapped on Chromosome 4 and identified as a null allele of Nhe1. Mutants show selective neuronal death in the cerebellum and brainstem but otherwise are healthy. This first example of a disease-causing mutation in an Nhe gene provides a new tool for studying the delicate balance of neuroexcitability and cell survival within the CNS.
“管家”型钠/氢交换体NHE1介导Na⁺和H⁺以1:1的比例通过质膜进行电中性交换。NHE1广泛存在，因其对细胞内pH值、细胞体积以及对生长因子的反应的调节作用而被广泛研究。我们描述了一种自发的小鼠突变体——慢波癫痫（swe），它具有包括共济失调在内的神经综合征以及由3次/秒失神发作和强直阵挛性发作组成的独特癫痫表型。swe被精细定位到4号染色体上，并被鉴定为Nhe1的无效等位基因。突变体在小脑和脑干中表现出选择性神经元死亡，但其他方面是健康的。Nhe基因中致病突变的这第一个例子为研究中枢神经系统内神经兴奋性和细胞存活的微妙平衡提供了一种新工具。
