Synaptic E3 ligase SCRAPPER in contextual fear conditioning: Extensive behavioral phenotyping of Scrapper heterozygote and overexpressing mutant mice

Ikuko Yao, Keizo Takao, Tsuyoshi Miyakawa, Seiji Ito, Mitsutoshi Setou

研究成果: Article査読

24 被引用数 (Scopus)

抄録

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 transgenic mice overexpressing SCRAPPER in the hippocampus did not show any significant difference in every test argued in this manuscript by comparison with wild-type mice. On the other hand, heterozygotes of Scrapper knockout [SCR (+/-)] mice showed significant difference in the contextual but not cued fear conditioning test. In addition, SCR (+/-) mice altered in some tests reflecting anxiety, which implies the loss of functions of SCRAPPER in the hippocampus. The behavioral phenotypes of Scrapper mutant mice suggest that molecular degradation conferred by SCRAPPER play important roles in hippocampal-dependent fear memory formation.

本文言語English
論文番号e17317
ジャーナルPloS one
6
2
DOI
出版ステータスPublished - 2011

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)
  • 農業および生物科学(全般)
  • 一般

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