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Original Article

Exp Neurobiol 2019; 28(4): 485-494

Published online August 31, 2019

© The Korean Society for Brain and Neural Sciences

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

Min Jung Kim1†, Ro Un Lee1†, Jihae Oh1, Ja Eun Choi1, Hyopil Kim1, Kyungmin Lee2, Su-Kyeong Hwang3, Jae-Hyung Lee4, Jin-A Lee5, Bong-Kiun Kaang1, Chae-Seok Lim6* and Yong-Seok Lee7*

1Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, 2Behavioral Neural Circuitry and Physiology Laboratory, Department of Anatomy, Brain Science & Engineering Institute, Kyungpook National University Graduate School of Medicine, Daegu 41944, 3Department of Pediatrics, Kyungpook National University Hospital, Daegu 41944, 4Department of Life and Nanopharmaceutical Sciences, Department of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, Seoul 02447, 5Department of Biotechnology and Biological Sciences, Hannam University, Daejeon 34430, 6Department of Pharmacology, Wonkwang University School of Medicine, Iksan 54538, 7Department of Physiology, Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea

Correspondence to: *To whom correspondence should be addressed.
Chae-Seok Lim, TEL: 82-63-850-6765, FAX: 82-63-850-7262
Yong-Seok Lee, TEL: 82-2-740-8225, FAX: 82-2-763-9667

†These authors equally contributed to this work.

Received: May 4, 2019; Revised: July 29, 2019; Accepted: July 30, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License( which permits unrestricted non-commercial use, distribution, andreproduction in any medium, provided the original work is properly cited.

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.

Graphical Abstract

Keywords: Vps13b, Cohen syndrome, Learning disability