Spectrum of social alterations in the Neurobeachin haploinsufficiency mouse model of autism.

Brain Research Bulletin
Paulien OdentRudi D'Hooge

Abstract

Autism spectrum disorder (ASD) is a common and pervasive neurodevelopmental disorder, characterized by sexually divergent social deficits. Its etiology is multifactorial with an important contribution of genetic factors. Neurobeachin (Nbea), a brain-enriched multidomain scaffolding protein, is an ASD candidate gene that was found to be translocated or deleted in ASD patients. Nbea haploinsufficient (+/-) mice have been proposed as an ASD mouse model, but its broad-spectrum social phenotype, sexual divergence and age-related robustness remain unstudied. This study compared one-year-old male and female Nbea+/- mice and their control littermates in an extensive behavioral battery that focused on social behaviors and communication. Nbea haploinsufficiency was associated with selective, sex-dependent, quantitative and qualitative changes, including alterations in social interest and approach, ultrasonic vocalization (USV) between same-sex adult conspecifics, and preferred types of social interaction. Notably, Nbea+/- females (but not males) displayed a significantly higher number of calls, and the mean principal frequency of their calls was higher than those of normal female littermates. Our results demonstrate that Nbea haploinsuff...Continue Reading

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