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 pH(i), cell volume, and response to growth factors. We describe a spontaneous mouse mutant, slow-wave epilepsy, (swe), with a neurological syndrome including ataxis 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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)