Protrudin-deficient mice manifest depression-like behavior with abnormalities in activity, attention, and cued fear-conditioning

Molecular Brain

Michiko Shirane¹  Yutaka Hashimoto²  Keiichi I. Nakayama²  Hiroyuki Katagiri³  Toshiya Manabe³  Shizuka Kobayashi³  Hirotaka Shoji⁴  Tsuyoshi Miyakawa⁴ 

[1] Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan;Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka, Japan;Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Tokyo, Japan;Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan;

关键词: Protrudin;    Knockout mouse;    Behavior;    Hyperactivity;    Depression;   

DOI  :  10.1186/s13041-020-00693-3

来源: Springer

【 摘 要 】

Protrudin is a protein that resides in the membrane of the endoplasmic reticulum and is highly expressed in the nervous system. Although mutations in the human protrudin gene (ZFYVE27, also known as SPG33) give rise to hereditary spastic paraplegia (HSP), the physiological role of the encoded protein has been largely unclear. We therefore generated mice deficient in protrudin and subjected them to a battery of behavioral tests designed to examine their intermediate phenotypes. The protrudin-deficient mice were found to have a reduced body size and to manifest pleiotropic behavioral abnormalities, including hyperactivity, depression-like behavior, and deficits in attention and fear-conditioning memory. They exhibited no signs of HSP, however, consistent with the notion that HSP-associated mutations of protrudin may elicit neural degeneration, not as a result of a loss of function, but rather as a result of a gain of toxic function. Overall, our results suggest that protrudin might play an indispensable role in normal neuronal development and behavior.

【 授权许可】

CC BY