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

Kirshenbaum, G.S.; Dachtler, J.; Roder, J.C.; Clapcote, S.J.

doi:10.1007/s10048-015-0461-1

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

Kirshenbaum, G.S.; Dachtler, J.; Roder, J.C.; Clapcote, S.J.

Authors

G.S. Kirshenbaum

J. Dachtler

J.C. Roder

S.J. Clapcote

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.

Citation

Kirshenbaum, G., Dachtler, J., Roder, J., & Clapcote, S. (2016). Transgenic rescue of phenotypic deficits in a mouse model of alternating hemiplegia of childhood. neurogenetics, 17(1), 57-63. https://doi.org/10.1007/s10048-015-0461-1

Journal Article Type	Article
Acceptance Date	Sep 16, 2015
Online Publication Date	Oct 13, 2015
Publication Date	Jan 1, 2016
Deposit Date	Apr 15, 2016
Publicly Available Date	May 3, 2016
Journal	neurogenetics
Print ISSN	1364-6745
Electronic ISSN	1364-6753
Publisher	Springer
Peer Reviewed	Peer Reviewed
Volume	17
Issue	1
Pages	57-63
DOI	https://doi.org/10.1007/s10048-015-0461-1

Files

Published Journal Article (445 Kb)
PDF

Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
© The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.