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

作者：Kirshenbaum Greer S; Idris Nagi F; Dachtler James; Roder John C; Clapcote Steven J^*

来源：Journal of Neurogenetics, 2016, 30(1): 42-49.

DOI：10.1080/01677063.2016.1182525

• Alternating hemiplegia of childhood
• ATP1A3
• mouse model
• social behavior

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 3 subunit, have been identified. To test the hypothesis that social behavioral deficits represent part of the phenotype of Na+, K+-ATPase 3 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 3 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.

• 出版日期2016
• 单位河北医科大学