SODIUM HYDROGEN EXCHANGER GENE DEFECT IN SLOW-WAVE EPILEPSY MUTANT MICE/

The ''housekeeping'' sodium/hydrogen exchanger, NHE1, mediates the ele ctroneutral 1:1 exchange of Na+ and H+ across the plasma membrane. NHE 1 is ubiquitous and is studied extensively for regulation of pH(i), ce ll volume, and response to growth factors. We describe a spontaneous m ouse mutant, slow-wave epilepsy, (swe), with a neurological syndrome i ncluding ataxia and a unique epilepsy phenotype consisting of 3/sec ab sence and tonic-clonic seizures. swe was fine-mapped on Chromosome 4 a nd identified as a null allele of Nhe1. Mutants show selective neurona l death in the cerebellum and brainstem but otherwise are healthy. Thi s 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.