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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Child
  • Disease Models, Animal*
  • Female
  • Genetic Therapy*
  • Hemiplegia / genetics*
  • Hemiplegia / pathology
  • Hemiplegia / therapy*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic*
  • Phenotype
  • Sodium-Potassium-Exchanging ATPase / genetics*
  • Treatment Outcome

Substances

  • Atp1a3 protein, mouse
  • Sodium-Potassium-Exchanging ATPase

Supplementary concepts

  • Alternating hemiplegia of childhood