Increased Level of RAB39B Leads to Neuronal Dysfunction and Behavioural Changes in Mice

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2023 Mar 28

PMID 36977207

Authors

Zijie Wang

Mengxi Niu

Naizhen Zheng

Jian Meng

Yiru Jiang

Dingting Yang

Peijie Yao

Tingting Yao

Hong Luo

Huaxi Xu

Yunlong Ge

Yun-Wu Zhang

Xian Zhang

Affiliations

Soon will be listed here.

Abstract

Duplications of the Xq28 region are a common cause of X-linked intellectual disability (XLID). The RAB39B gene locates in Xq28 and has been implicated in disease pathogenesis. However, whether increased dosage of RAB39B leads to cognitive impairment and synaptic dysfunction remains elusive. Herein, we overexpressed RAB39B in mouse brain by injecting AAVs into bilateral ventricles of neonatal animals. We found that at 2 months of age, neuronal overexpression of RAB39B impaired the recognition memory and the short-term working memory in mice and resulted in certain autism-like behaviours, including social novelty defect and repetitive grooming behaviour in female mice. Moreover, overexpression of RAB39B decreased dendritic arborization of primary neurons in vitro and reduced synaptic transmission in female mice. Neuronal overexpression of RAB39B also altered autophagy without affecting levels and PSD distribution of synaptic proteins. Our results demonstrate that overexpression of RAB39B compromises normal neuronal development, thereby resulting in dysfunctional synaptic transmission and certain intellectual disability and behavioural abnormalities in mice. These findings identify a molecular mechanism underlying XLID with increased copy numbers of Xq28 and provide potential strategies for disease intervention.

Citing Articles

Increased level of RAB39B leads to neuronal dysfunction and behavioural changes in mice.

Wang Z, Niu M, Zheng N, Meng J, Jiang Y, Yang D J Cell Mol Med. 2023; 27(9):1214-1226.

PMID: 36977207 PMC: 10148058. DOI: 10.1111/jcmm.17704.

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