title: Transgenic rescue of phenotypic deficits in a mouse model of alternating hemiplegia of childhood.
abstract: Missense mutations in ATP1A3 encoding Na(+),K(+)-ATPase α3 are the primary cause of alternating hemiplegia of childhood (AHC). Most ATP1A3 mutations in AHC lie within a cluster in or near transmembrane α-helix TM6, including I810N that is also found in the Myshkin mouse model of AHC. These mutations all substantially reduce Na(+),K(+)-ATPase α3 activity. Herein, we show that Myshkin mice carrying a wild-type Atp1a3 transgene that confers a 16 % increase in brain-specific total Na(+),K(+)-ATPase activity show significant phenotypic improvements compared with non-transgenic Myshkin mice. Interventions to increase the activity of wild-type Na(+),K(+)-ATPase α3 in AHC patients should be investigated further.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University Avenue, Toronto, ON, M5G 1X5, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A8, Canada.
authors.forename: Greer S
authors.initials: GS
authors.lastname: Kirshenbaum
authors.affiliation: School of Biomedical Sciences, Garstang Building, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: James
authors.initials: J
authors.lastname: Dachtler
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University Avenue, Toronto, ON, M5G 1X5, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A8, Canada.
authors.forename: John C
authors.initials: JC
authors.lastname: Roder
authors.affiliation: School of Biomedical Sciences, Garstang Building, University of Leeds, Leeds, LS2 9JT, UK. s.j.clapcote@leeds.ac.uk.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Clapcote
mesh_terms: D000818:Animals; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006429:Hemiplegia / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C526097:Atp1a3 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Alternating hemiplegia; Atp1a3; Mice; Na+,K+-ATPase α3; Transgenic rescue