synaptic e3 ligase scrapper in contextual fear conditioning extensive behavioral phenotyping of scrapper heterozygote and overexpressing mutant mice突触e3连接酶拳击手在上下文恐惧条件反射行为表型出现广泛的拳击手杂合子和overexpressing突变老鼠.pdf

Synaptic E3 Ligase SCRAPPER in Contextual Fear Conditioning: Extensive Behavioral Phenotyping of Scrapper Heterozygote and Overexpressing Mutant Mice 1,2 3,4 3,4,5 1 2,6 Ikuko Yao *, Keizo Takao , Tsuyoshi Miyakawa , Seiji Ito , Mitsutoshi Setou * 1 Department of Medical Chemistry, Kansai Medical University, Moriguchi, Osaka, Japan, 2 Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo, Japan, 3 Genetic Engineering and Functional Genomics Group, Frontier Technology Center, Graduate School of Medicine Kyoto University, Kyoto, Japan, 4 Section of Behavior Analysis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan, 5 Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan, 6 Department of Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan Abstract SCRAPPER, an F-box protein coded by FBXL20, is a subunit of SCF type E3 ubiquitin ligase. SCRAPPER localizes synapses and directly binds to Rab3-interacting molecule 1 (RIM1), an essential factor for synaptic vesicle release, thus it regulates neural transmission via RIM1 degradation. A defect in SCRAPPER leads to neurotransmission abnormalities, which could subsequently result in neurodegenerative phenotypes. Because it is likely that the alteration of neural transmission in Scrapper mutant mice affect their systemic condition, we have analyzed the behavioral phenotypes of mice with decreased or increased the amount of SCRAPPER. We carried out a series of behavioral test batteries for Scrapper mutant mice. Scrapper