Impairment of social behavior and communication in mice lacking the Uba6-dependent ubiquitin activation system

•Uba6 brain-specific knockout (termed NKO) mice are a valid autism mouse model.•NKO mice exhibit social impairments.•NKO mice display reduced vocalizations.

The Uba6–Use1 ubiquitin enzyme cascade is a poorly understood arm of the ubiquitin–proteasome system required for mouse development. Recently, we reported that Uba6 brain-specific knockout (termed NKO) mice display abnormal social behavior and neuronal development due to a decreased spine density and accumulation of Ube3a and Shank3. To better characterize a potential role for NKO mice in autism spectrum disorders (ASDs), we performed a comprehensive behavioral characterization of the social behavior and communication of NKO mice. Our behavioral results confirmed that NKO mice display social impairments, as indicated by fewer vocalizations and decreased social interaction. We conclude that UBA6 NKO mice represent a novel ASD mouse model of anti-social and less verbal behavioral symptoms.