GPR50敲除导致小鼠神经元数目和发育异常研究

摘要

Objective:To investigate whether G protein-coupled receptor 50 (GPR50) has an effect on brain development .Methods:GPR50 knockout (GPR50 KO) mice and their littermates were used in this study .We first-ly analyzed the GPR50 expression in wild type (WT ) mice at different developmental stages by western blotting . Then ,we investigated the number of deeper and upper layer neurons in neocortex and the number of hippocampal in-terneurons in GPR50 KO mice at P1 by immunofluorescence .Results :Our data indicated that GPR50 exhibits strong expression in the developing brains .Increased number of clretinin positive interneurons were observed in hippocam-pus of GPR50 KO mice ,whereas the number of both deeper and uppers layers neurons in neocortex show similar level between WT and GPR50 KO mice .Additionally ,we found abnormal apical dendrite orientation of pyramidal neurons in GPR50 KO mice neocortex nearby the madeleine of two hemispheres by Golgi staining .Conclusion :GPR50 plays vital roles in the brain durin development .%目的:探讨G蛋白偶联受体50(G PR50)在大脑发育中的作用.方法:利用G PR50基因敲除小鼠和其同窝野生型小鼠(WT),通过Western blot检测了GPR50在发育的不同阶段的表达情况.利用免疫荧光实验分析了P1时期G PR50敲除对皮层深层和浅层神经元数目的影响以及对海马区中间神经元的影响.结果:GPR50在发育阶段有较高的表达,与WT组小鼠相比,GPR50敲除不影响皮层深层和浅层的神经元的数目,却导致海马区钙网膜蛋白(Calretintin,CR)阳性中间神经元数目显著增多.最后,成年小鼠脑的高尔基染色实验结果表明:GPR50敲除小鼠皮层锥体神经元的顶树突方向紊乱.结论:G PR50在神经发育中起重要作用.