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

Yao I, Takao K, Miyakawa T, Ito S, Setou M - PLoS ONE (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Chemistry, Kansai Medical University, Moriguchi, Osaka, Japan. yaoik@takii.kmu.ac.jp

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 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.

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Related in: MedlinePlus

Increased social interaction activity in home cage in SCR (+/−) mice.Social interaction test in home cage: mean number of particles detected and activity level were recorded over 6 days. The graph shows the mean values of those recorded in the middle 3days. (*) The activity of mutant mice increased significantly throughout the dark period. The p values indicate genotype effect in two-way repeated measures ANOVA.
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pone-0017317-g006: Increased social interaction activity in home cage in SCR (+/−) mice.Social interaction test in home cage: mean number of particles detected and activity level were recorded over 6 days. The graph shows the mean values of those recorded in the middle 3days. (*) The activity of mutant mice increased significantly throughout the dark period. The p values indicate genotype effect in two-way repeated measures ANOVA.

Mentions: To understand the physiological role of SCRAPPER in the adult brain, we generated Scrapper gene-deficient and Scrapper gene-overexpressing mice [1]. Because of the lethality of C57/BL6J backcrossed mutant mice, we analyzed heterozygous Scrapper gene-deficient mice [SCR (+/−)] using behavioral test battery. Western blot analysis showed a reduction of about 50% in SCR (+/−) whole brain lysates as described in our earlier report [1]. SCR (+/−) mice were almost the same size as the wild-type (WT) mice and were fertile, and grossly healthy; however, some heterozygous and KO mice died suddenly in the early postnatal period from unknown reasons [1]. The body weight and temperature of the SCR (+/−) mice used in this study were almost the same as those of WT mice (Table 1).


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

Yao I, Takao K, Miyakawa T, Ito S, Setou M - PLoS ONE (2011)

Increased social interaction activity in home cage in SCR (+/−) mice.Social interaction test in home cage: mean number of particles detected and activity level were recorded over 6 days. The graph shows the mean values of those recorded in the middle 3days. (*) The activity of mutant mice increased significantly throughout the dark period. The p values indicate genotype effect in two-way repeated measures ANOVA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3044740&req=5

pone-0017317-g006: Increased social interaction activity in home cage in SCR (+/−) mice.Social interaction test in home cage: mean number of particles detected and activity level were recorded over 6 days. The graph shows the mean values of those recorded in the middle 3days. (*) The activity of mutant mice increased significantly throughout the dark period. The p values indicate genotype effect in two-way repeated measures ANOVA.
Mentions: To understand the physiological role of SCRAPPER in the adult brain, we generated Scrapper gene-deficient and Scrapper gene-overexpressing mice [1]. Because of the lethality of C57/BL6J backcrossed mutant mice, we analyzed heterozygous Scrapper gene-deficient mice [SCR (+/−)] using behavioral test battery. Western blot analysis showed a reduction of about 50% in SCR (+/−) whole brain lysates as described in our earlier report [1]. SCR (+/−) mice were almost the same size as the wild-type (WT) mice and were fertile, and grossly healthy; however, some heterozygous and KO mice died suddenly in the early postnatal period from unknown reasons [1]. The body weight and temperature of the SCR (+/−) mice used in this study were almost the same as those of WT mice (Table 1).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Chemistry, Kansai Medical University, Moriguchi, Osaka, Japan. yaoik@takii.kmu.ac.jp

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 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.

Show MeSH
Related in: MedlinePlus