Exp Neurobiol.  2019 Aug;28(4):485-494. 10.5607/en.2019.28.4.485.

Spatial Learning and Motor Deficits in Vacuolar Protein Sorting-associated Protein 13b (Vps13b) Mutant Mouse

• Kim MJ
• Lee RU
• Oh J
• Choi JE
• Kim H
• Lee K
• Hwang SK
• Lee JH
• Lee JA
• Kaang BK
• Lim CS
• Lee YS

• KMID: 2458546
• DOI: http://doi.org/10.5607/en.2019.28.4.485

Abstract

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 VPS13B gene are associated with Cohen syndrome and other cognitive disorders such as intellectual disabilities and autism spectrum disorder (ASD). However, the patho-physiology of VPS13B-associated cognitive deficits is unclear, in part, due to the lack of animal models. Here, we generated a Vps13b exon 2 deletion mutant mouse and analyzed the behavioral phenotypes. We found that Vps13b 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 Vps13b mutant mice showed deficits in spatial learning in the hidden platform version of the Morris water maze. The Vps13b mutant mice were normal in other behaviors such as anxiety-like behaviors, working memory and social behaviors. Our results suggest that Vps13b mutant mice may recapitulate key clinical symptoms in Cohen syndrome such as intellectual disability and hypotonia. Vps13b mutant mice may serve as a useful model to investigate the pathophysiology of VPS13B-associated disorders.

Keyword

Vps13b; Cohen syndrome; Learning disability

MeSH Terms

Animals
Autism Spectrum Disorder
Cognition Disorders
Exons
Humans
Intellectual Disability
Learning Disorders
Memory, Short-Term
Mice*
Models, Animal
Muscle Hypotonia
Phenotype
Rotarod Performance Test
Social Behavior
Spatial Learning*
Water
Water