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Neurogenetics. 2016 Jan;17(1):57-63. doi: 10.1007/s10048-015-0461-1. Epub 2015 Oct 13.

Transgenic rescue of phenotypic deficits in a mouse model of alternating hemiplegia of childhood.

Author information

1
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University Avenue, Toronto, ON, M5G 1X5, Canada.
2
Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A8, Canada.
3
School of Biomedical Sciences, Garstang Building, University of Leeds, Leeds, LS2 9JT, UK.
4
School of Biomedical Sciences, Garstang Building, University of Leeds, Leeds, LS2 9JT, UK. s.j.clapcote@leeds.ac.uk.

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.

KEYWORDS:

Alternating hemiplegia; Atp1a3; Mice; Na+,K+-ATPase α3; Transgenic rescue

PMID:
26463346
PMCID:
PMC4701769
DOI:
10.1007/s10048-015-0461-1
[Indexed for MEDLINE]
Free PMC Article

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