The discovery of novel gene for stabilizing wakefulness

• Published in: Proceedings for Annual Meeting of The Japanese Pharmacological Society Vol. 92; p. 3-P-035
• Main Authors: Ono, Hiroaki, Yamada, Rikuhiro, Shi, Shoi, Ukai-Tadenuma, Maki, Fujishima, Hiroshi, Ukai, Hideki, Ohno, Rei-ichiro, Tone, Daisuke, Kanda, Genki, Kon, Kazuhiro, Ueda, Hiroki
• Format: Journal Article
• Language: Japanese; English
• Published: Japanese Pharmacological Society 2019
• ISSN: 2435-4953; 2435-4953
• DOI: 10.1254/jpssuppl.92.0_3-P-035

Sleep is regulated through intricate communication among specialized neurons in the brain. While neuromodulators and their receptors have been extensively studied, the second messenger systems downstream of the receptors remained largely uncharted. Genetic manipulation is a powerful tool to investigate the function of specific components in a system, but often it is unfeasible to use conventional reverse genetics to examine genes in a comprehensive manner. Here, we used a triple-CRISPR method to efficiently produce whole-body biallelic knockout (KO) mice, and found that gene X KO mice had an increased duration of NREM sleep. Furthermore, gene X KO mice exhibited NREM sleep accompanied by body tremors and/or occasional limb movements. Behavioral experiments revealed that gene X KO mice exhibited disturbance in motor coordination and balance. In vitro reconstruction assay revealed that protein X (protein encoded by gene X) enhanced Ca2+ pump activity. Subsequent AAV-mediated protein X overexpression in vivo increased wake duration. These results imply a role for gene X in consolidating a behavioral state and a potential molecular mechanism for NREM parasomnia.