Understanding of regulatory mechanism of motor activity using D1 and D2 dopamine receptor gene-modified mice

使用 D1 和 D2 多巴胺受体基因修饰小鼠了解运动活动的调节机制

• 批准号: 22500343
• 负责人: SASAOKA Toshikuni
• 金额: $ 2.33万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22500343/
• 关键词: ドーパミン受容体; 遺伝子操作マウス; パーキンソン病; 運動調節; 協調運動; 学習記憶; 遺伝子工学; 運動制御; 大脳基底核; 遺伝子操作動物; マウス; 発生工学; ドキシサイクリン

In Parkinson disease the degeneration of nigro-striatal dopamine neuron leads to depletion of dopamine and motor deficit. It is known that D1 and D2 dopamine receptors (D1R, D2R) expressed in the medium spiny neurons of striatum are involved to motor control. However, the regulatory mechanism of motor control via D1R and D2R remains to be clarified. In this study we found the conditional D1R-expressing mice controlled by Tet-off system showed decrease of motor activity in the homecage when D1R expression was suppressed in adult stage. This finding was opposite to the marked increase of motor activity of D1R KO mice. These suggest the presence or absence of D1R expression during mouse development is closely related to up-regulation or down-regulation of motor activity in adult stage.

在帕金森病中，黑质纹状体多巴胺神经元的退化导致多巴胺的耗竭和运动障碍。已知纹状体中棘神经元表达的D_1和D_2多巴胺受体(D_1R、D_2R)参与运动控制。然而，D1R和D2R对运动控制的调控机制尚不清楚。在本研究中，我们发现由Tet-Off系统控制的条件性表达D1R的小鼠在成年期抑制D1R表达时，在家庭中的运动活动减少。这一发现与D1R KO小鼠运动活动的显著增加相反。提示D1R在小鼠发育过程中表达的存在或缺失与成体阶段运动活动的上调或下调密切相关。

项目成果

A molecular genetic approach to uncovering the differential functions of dopamine D2 receptor isoforms.

揭示多巴胺 D2 受体亚型差异功能的分子遗传学方法。

• DOI: 10.1007/978-1-62703-251-3_11
• 发表时间: 2013
• 期刊: Methods in Molecular Biology
• 作者: 浜之上 誠;森岡 和仁;緒方 徹;中嶋 一行;高松 研;Wang Yanyan
• 通讯作者: Wang Yanyan

Dopamine D1 and D2 receptors differently modulate information processing through the basal ganglia

多巴胺 D1 和 D2 受体通过基底神经节不同地调节信息处理

• 发表时间: 2012
• 作者: Chiken S;Ohta C;Sato A;Sasaoka T;Kurokawa M;Nambu A
• 通讯作者: Nambu A

ドーパミンD1およびD2受容体ノックアウトマウスにおける行動および線条体GABA性シナプス伝達の解析Analyses of motor activity and striatal GABAergic synaptic transmission in dopamine D1 and D2 receptor knock-out mice

多巴胺 D1 和 D2 受体敲除小鼠的运动活动和纹状​​体 GABA 能突触传递分析

• 发表时间: 2011
• 作者: 籾山俊彦;佐藤朝子;勝木元也;笹岡俊邦
• 通讯作者: 笹岡俊邦

Abnormal Epithelial Cell Polarity and Ectopic Epidermal Growth Factor Receptor (EGFR) Expression Induced in Emx2 KO Embryonic Gonads

• DOI: 10.1210/en.2010-0915
• 发表时间: 2010-12-01
• 期刊: ENDOCRINOLOGY
• 影响因子: 4.8
• 作者: Kusaka, Masatomo;Katoh-Fukui, Yuko;Morohashi, Ken-ichirou
• 通讯作者: Morohashi, Ken-ichirou

Methyl CpG-binding Protein Isoform MeCP2_e2 Is Dispensable for Rett Syndrome Phenotypes but Essential for Embryo Viability and Placenta Development

• DOI: 10.1074/jbc.m111.309864
• 发表时间: 2012-04-20
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Itoh, Masayuki;Tahimic, Candice G. T.;Kurimasa, Akihiro
• 通讯作者: Kurimasa, Akihiro