Deficits in social behavioral tests in a mouse model of alternating hemiplegia of childhood.

Abstract

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.

• Authors: Greer S Kirshenbaum, Nagi F Idris, James Dachtler, John C Roder, Steven J Clapcote
• Journal: Journal of neurogenetics (J Neurogenet) Vol. 30 Issue 1 Pg. 42-9 (03 2016) ISSN: 1563-5260 [Electronic] England
• PMID: 27276195 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Behavior, Animal
• Disease Models, Animal
• Hemiplegia
• Mice
• Mice, Mutant Strains