Spatial Learning and Motor Deficits in () Mutant Mouse.

Vacuolar protein sorting-associated protein 13B (VPS13B), also known as COH1, is one of the VPS13 family members which is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Mutations in the gene are associated with Cohen syndrome and other cognitive disorders such as intellectual disabilities and autism spectrum disorder (ASD). However, the pathophysiology of VPS13B-associated cognitive deficits is unclear, in part, due to the lack of animal models. Here, we generated a exon 2 deletion mutant mouse and analyzed the behavioral phenotypes. We found that mutant mice showed reduced activity in open field test and significantly shorter latency to fall in the rotarod test, suggesting that the mutants have motor deficits. In addition, we found that mutant mice showed deficits in spatial learning in the hidden platform version of the Morris water maze. The mutant mice were normal in other behaviors such as anxiety-like behaviors, working memory and social behaviors. Our results suggest that mutant mice may recapitulate key clinical symptoms in Cohen syndrome such as intellectual disability and hypotonia. mutant mice may serve as a useful model to investigate the pathophysiology of -associated disorders.