Sodium/hydrogen exchanger gene defect in slow-wave epilepsy mutant mice

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ataxia
  • Brain Chemistry
  • Cell Line
  • Cerebellum / pathology
  • Cerebral Cortex / physiopathology
  • Chromosome Mapping
  • Crosses, Genetic
  • Electroencephalography
  • Epilepsy / genetics*
  • Epilepsy / metabolism
  • Epilepsy / pathology
  • Epilepsy / physiopathology*
  • Fibroblasts
  • Genes, Recessive
  • Ion Transport
  • Mice
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants / genetics*
  • Organ Specificity
  • Phenotype
  • Point Mutation / genetics
  • RNA / analysis
  • Sodium / metabolism
  • Sodium-Hydrogen Exchangers / analysis
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / physiology*


  • Sodium-Hydrogen Exchangers
  • growth factor-activatable Na-H exchanger NHE-1
  • RNA
  • Sodium