title: Sodium/hydrogen exchanger gene defect in slow-wave epilepsy mutant mice.
abstract: 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.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Cox
authors.forename: C M
authors.initials: CM
authors.lastname: Lutz
authors.forename: C L
authors.initials: CL
authors.lastname: Yang
authors.forename: D
authors.initials: D
authors.lastname: Biemesderfer
authors.forename: R T
authors.initials: RT
authors.lastname: Bronson
authors.forename: A
authors.initials: A
authors.lastname: Fu
authors.forename: P S
authors.initials: PS
authors.lastname: Aronson
authors.forename: J L
authors.initials: JL
authors.lastname: Noebels
authors.forename: W N
authors.initials: WN
authors.lastname: Frankel
mesh_terms: D000818:Animals; D001259:Ataxia; D001923:Brain Chemistry; D002460:Cell Line; D002531:Cerebellum / Q000473:pathology; D002540:Cerebral Cortex / Q000503:physiopathology; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005347:Fibroblasts; D005808:Genes, Recessive; D017136:Ion Transport; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000235:genetics*; D009928:Organ Specificity; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D012313:RNA / Q000032:analysis; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D012313:RNA; D012964:Sodium