Deficits in social behavioral tests in a mouse model of alternating hemiplegia of childhood.
Social behavioral deficits have been observed in patients diagnosed with alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism and CAPOS syndrome, in which specific missense mutations in ATP1A3, encoding the Na(+), K(+)-ATPase α3 subunit, have been identified. To test the hypothesis that social behavioral deficits represent part of the phenotype of Na(+), K(+)-ATPase α3 mutations, we assessed the social behavior of the Myshkin mouse model of AHC, which has an I810N mutation identical to that found in an AHC patient with co-morbid autism. Myshkin mice displayed deficits in three tests of social behavior: nest building, pup retrieval and the three-chamber social approach test. Chronic treatment with the mood stabilizer lithium enhanced nest building in wild-type but not Myshkin mice. In light of previous studies revealing a broad profile of neurobehavioral deficits in the Myshkin model - consistent with the complex clinical profile of AHC - our results suggest that Na(+), K(+)-ATPase α3 dysfunction has a deleterious, but nonspecific, effect on social behavior. By better defining the behavioral profile of Myshkin mice, we identify additional ATP1A3-related symptoms for which the Myshkin model could be used as a tool to advance understanding of the underlying neural mechanisms and develop novel therapeutic strategies.
a Lunenfeld-Tanenbaum Research Institute , Mount Sinai Hospital , University Avenue , Toronto , Canada ;|b Institute of Medical Science, University of Toronto , Toronto , Canada ;
Greer S
GS
Kirshenbaum
c School of Biomedical Sciences , University of Leeds , Leeds , UK.
Nagi F
NF
Idris
c School of Biomedical Sciences , University of Leeds , Leeds , UK.
James
J
Dachtler
a Lunenfeld-Tanenbaum Research Institute , Mount Sinai Hospital , University Avenue , Toronto , Canada ;|b Institute of Medical Science, University of Toronto , Toronto , Canada ;
John C
JC
Roder
c School of Biomedical Sciences , University of Leeds , Leeds , UK.
Steven J
SJ
Clapcote
D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D006429:Hemiplegia; D051379:Mice; D008817:Mice, Mutant Strains
ATP1A3; mouse model; Alternating hemiplegia of childhood; social behavior