日本群马大学应用生理学副教授下川哲昭日前宣布，他与德国同行联合研究发现，如果参与神经传导的一种基因不能有效发挥作用，实验鼠就会出现与人类多动症类似的症状。
研究人员发现，如果基因“CIN85”异常，实验鼠就会出现“好动”症状，其活动速度加快，移动的距离也加长。研究人员认为，基因异常使神经处于持续受刺激状态，这是造成实验鼠多动的原因。
下川哲昭说，导致人类多动症的原因可能更加复杂，如可能不是一种而是多种基因异常造成的。他希望新发现能够有助于破解多动症的发病机制，最终开发出更加有效的治疗药物。
相关英文文献阅读：
The EMBO Journal , () | doi:10.1038/emboj.2010.120
CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice
Noriaki Shimokawa, Kaisa Haglund, Sabine M Hölter, Caroline Grabbe, Vladimir Kirkin, Noriyuki Koibuchi, Christian Schultz, Jan Rozman, Daniela Hoeller, Chun-Hong Qiu, Marina B Londoño, Jun Ikezawa, Peter Jedlicka, Birgit Stein, Stephan W Schwarzacher, David P Wolfer, Nicole Ehrhardt, Rainer Heuchel, Ioannis Nezis, Andreas Brech, Mirko H H Schmidt, Helmut Fuchs, Valerie Gailus-Durner, Martin Klingenspor, Oliver Bogler, Wolfgang Wurst, Thomas Deller, Martin Hrabé de Angelis and Ivan Dikic
Abstract
Despite extensive investigations of Cbl-interacting protein of 85 kDa (CIN85) in receptor trafficking and cytoskeletal dynamics, little is known about its functions in vivo. Here, we report the study of a mouse deficient of the two CIN85 isoforms expressed in the central nervous system, exposing a function of CIN85 in dopamine receptor endocytosis. Mice lacking CIN85 exon 2 (CIN85Δex2) show hyperactivity phenotypes, characterized by increased physical activity and exploratory behaviour. Interestingly, CIN85Δex2 animals display abnormally high levels of dopamine and D2 dopamine receptors (D2DRs) in the striatum, an important centre for the coordination of animal behaviour. Importantly, CIN85 localizes to the post-synaptic compartment of striatal neurons in which it co-clusters with D2DRs. Moreover, it interacts with endocytic regulators such as dynamin and endophilins in the striatum. Absence of striatal CIN85 causes insufficient complex formation of endophilins with D2DRs in the striatum and ultimately decreased D2DR endocytosis in striatal neurons in response to dopamine stimulation. These findings indicate an important function of CIN85 in the regulation of dopamine receptor functions and provide a molecular explanation for the hyperactive behaviour of CIN85Δex2 mice.
