Functional analysis of Alivin1/Amigo2

Alivin1/Amigo2的功能分析

• 批准号: 16500253
• 负责人: ONO Tomio
• 金额: $ 2.54万
• 依托单位: Tokyo metropolitan organization for Medical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16500253/
• 关键词: apoptosis; Alivin; neuronal activity; Alzheimer's disease; neuronal cell death; cerebellar granule neurons; leucine rich repeat; immunoglobulin

Alivin1/Amigo2 is a neuronal activity-dependent gene that is a potential therapeutic target for neurodegenerative diseases. This gene was originally discovered by us (1) and has been shown to be involved in neuronal activity-dependent suppression of apoptosis, cell adhesion, migration, and carcinogenesis. Alivin1 encodes a transmembrane protein that has 6.5 times leucine-rich repeats (LRR) and one immunoglobulin (IG) domain. The encoded protein is assumed to interact with its binding partner (s) through these LRR and IG domains and involve in the signal transduction (s) for survival. In order to study biological functions of alivin 1 in mice, we generated the knockout mouse line. Open-field tests were carried out twice with a week interval using the same subjects of alivin1(-/-) and wild type mice (WT). The primary open-field tests showed that the per cent time spent in the central area of the field of alivin1 (-/-) mice was larger than that of WT, suggesting that alivin 1 (-/-) mice have reduced fear and anxiety compared to WT. The comparison between the results of the primary and the secondary tests showed that the locomotor activity of alivin1 (-/-) mice under the familiar environment was larger than that of WT. Alivin1 (-/-) mice kept in their home cages also showed higher locomotor activity than WT. These results suggest that deficiency in alivin1 is associated with enhanced locomotor activity and reduced fear and anxiety.(1) Ono et al.J.Neurosci.23, 5887-5896, 2003.

Alivin 1/Amigo 2是一个神经元活性依赖性基因，是神经退行性疾病的潜在治疗靶点。该基因最初由我们发现（1），并已被证明参与神经元活性依赖性抑制细胞凋亡、细胞粘附、迁移和致癌。Alivin 1编码一种跨膜蛋白，具有6.5倍的富含亮氨酸重复序列（LRR）和一个免疫球蛋白（IG）结构域。编码的蛋白质被认为通过这些LRR和IG结构域与其结合伴侣相互作用，并参与生存的信号转导。为了研究alivin 1基因在小鼠体内的生物学功能，我们建立了alivin 1基因敲除小鼠品系。使用相同的alivin 1（-/-）和野生型小鼠（WT）受试者进行两次旷场试验，间隔一周。初步旷场试验显示，在alivin 1（-/-）小鼠旷场中心区域花费的时间百分比大于WT，表明与WT相比，alivin 1（-/-）小鼠的恐惧和焦虑减少。初次和二次实验结果的比较表明，alivin 1（-/-）小鼠在熟悉环境下的运动活动大于WT小鼠。保持在其家笼中的Alivin 1（-/-）小鼠也显示出比WT更高的运动活动。这些结果表明，缺乏alivin 1与增强运动活动和减少恐惧和焦虑有关。(1)Ono et al.J.Neurosci.23，5887-5896，2003.

项目成果

Mice deficient in alivin1/amigo2 show enhanced locomotor activity and reduced fear and anxiety

缺乏alivin1/amigo2的小鼠表现出增强的运动活动以及减少的恐惧和焦虑

• 发表时间: 2008
• 作者: Ono;T.;Akamatsu;N.;Shitara;H.;Ishii;R.;Taya;C.;Yamada;I.;Shibukawa;Y.;Kushida;T.;Furuse;T.;Watabe;K.;Wakana;S.;Yonekawa;H.
• 通讯作者: H.

新規のrhoGEF遺伝子は初代培養小脳顆粒神経細胞のアポトーシスのコミットメント時間に同期して-過性に発現する.

一种新的 rhoGEF 基因与原代培养的小脑颗粒神经元的凋亡承诺时间同步过度表达。

• 发表时间: 2005
• 作者: 小野富男;米川博通:
• 通讯作者: 米川博通:

A novel rho gene is regulated by neuronal activity and transiently up-regulated concomitant with commitment time of apoptosis of primary cultured cerebellar granule neurons

一种新型 rho 基因受神经元活动调节，并随着原代培养的小脑颗粒神经元凋亡的承诺时间而短暂上调

• 发表时间: 2005
• 作者: Ono;T.;Yonekawa;H.
• 通讯作者: H.

Mice deficient in alivin1/amigo2 show enhanced locomotor activity and reduced fear and anxiety.

缺乏alivin1/amigo2的小鼠表现出增强的运动活动以及减少的恐惧和焦虑。

• 发表时间: 2008
• 作者: Ono,T.;Akamatsu,N.;Shitara,H.;Ishii,R.;Taya,C.;Yamada,I.;Shibukawa,Y.;Kushida,T.;Furuse,T.;Watabe,K.;Wakana,S.;Yonekawa,H.
• 通讯作者: Yonekawa,H.

Hippocalcin protects hippocampal neurons against excitotoxin damage by enhancing calcium extrusion

• DOI: 10.1016/j.neuroscience.2006.12.011
• 发表时间: 2007-03-16
• 期刊: NEUROSCIENCE
• 影响因子: 3.3
• 作者: Masuo, Y.;Ogura, A.;Takamatsua, K.
• 通讯作者: Takamatsua, K.