Ichise T, Kano M, Hashimoto K, Yanagihara D, Nakao K, Shigemoto R, Katsuki M, Aiba A
Laboratory of DNA Biology and Embryo Engineering, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Science. 2000 Jun 9;288(5472):1832-5. doi: 10.1126/science.288.5472.1832.
Targeted deletion of metabotropic glutamate receptor-subtype 1 (mGluR1) gene can cause defects in development and function in the cerebellum. We introduced the mGluR1alpha transgene into mGluR1-null mutant [mGluR1 (-/-)] mice with a Purkinje cell (PC)-specific promoter. mGluR1-rescue mice showed normal cerebellar long-term depression and regression of multiple climbing fiber innervation, events significantly impaired in mGluR1 (-/-) mice. The impaired motor coordination was rescued by this transgene, in a dose-dependent manner. We propose that mGluR1 in PCs is a key molecule for normal synapse formation, synaptic plasticity, and motor control in the cerebellum.
对代谢型谷氨酸受体1型(mGluR1)基因进行靶向缺失会导致小脑发育和功能出现缺陷。我们用浦肯野细胞(PC)特异性启动子将mGluR1α转基因导入mGluR1基因缺失的突变体[mGluR1(-/-)]小鼠中。mGluR1拯救小鼠表现出正常的小脑长时程抑制以及多条攀爬纤维支配的消退,而这些事件在mGluR1(-/-)小鼠中显著受损。这种转基因以剂量依赖的方式拯救了受损的运动协调性。我们提出,浦肯野细胞中的mGluR1是小脑正常突触形成、突触可塑性和运动控制的关键分子。