TY - JOUR
T1 - Synaptic E3 ligase SCRAPPER in contextual fear conditioning
T2 - Extensive behavioral phenotyping of Scrapper heterozygote and overexpressing mutant mice
AU - Yao, Ikuko
AU - Takao, Keizo
AU - Miyakawa, Tsuyoshi
AU - Ito, Seiji
AU - Setou, Mitsutoshi
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79952091055&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952091055&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0017317
DO - 10.1371/journal.pone.0017317
M3 - Article
C2 - 21390313
AN - SCOPUS:79952091055
VL - 6
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e17317
ER -