Analysis of the molecular bases on the stress sensitivity and abnormal emotional function in the developmental process of Fyn-deficient mice.

fynn -酪氨酸激酶缺陷小鼠的情绪功能和神经发育缺陷的分子机制被研究为基于明显分子缺陷的发育障碍模型。主要分析了新皮质生成缺陷、抗精神病药物反应异常、杏仁核功能缺陷以及杏仁核的发育机制。Fyn在新皮质发生中的功能分析：在Fyn缺乏的情况下，证实了II-III层的形成有缺陷，并明确了Fyn的表达，很好地对应了II-III层神经元的产生和迁移阶段。在II-III层神经发生阶段，通过子宫内电穿孔将fyn基因转移到fyn缺乏症新皮层原基的神经上皮中，部分挽救了皮层神经元迁移和分层缺陷。在新皮质形成过程中，也证实了黏附激酶参与f_more n信号转导通路。纹状体中Fyn的功能分析：Fyn缺乏表现出对抗精神病药物如氟哌啶醇（一种多巴胺D2受体拮抗剂）的异常反应。体内和体外分析发现氟哌啶醇激活Fyn，激活的Fyn刺激NMDA受体NR2B亚基酪氨酸磷酸化，从而增强NMDA受体通道活性和纹状体神经元的兴奋性。杏仁核Fyn功能分析：由于Fyn缺乏症杏仁核对NMDA处理反应异常，因此在NMDA处理后，对对照组与Fyn缺乏症杏仁核基因表达差异进行综合分析。激光捕获显微解剖和cDNA阵列分析显示，Swim6基因在Fyn缺乏症的杏仁核中央核中显著下调。结果表明，Swim6与MAPK信号转导通路存在功能偶联。少

The molecular mechanisms of defective emotional functions and neural development as found in the Fyn-tyrosine-kinase-deficient mice were investigated as a model for developmental disorders based on the distinct molecular defect. The defective neocorticogenesis, abnormal response to anti-psychotics and the defective function of amygdala were mainly analysed as well as the developmental mechanisms of amygdala.1. Functional analysis of Fyn in the neocorticogenesis: the formation of the layers II-III was demonstrated to be defective in the Fyn deficiency, and the expression of Fyn was made clear to well correspond to the stage of generation and migration of the layer II-III neurons. The transfer of fyn gene into the neuroepithelium of the neocortical primordium of Fyn deficiency by in utero electroporation at the stage of neurogenesis of the layers II-III partially rescued the defective migration and stratification of the cortical neurons. The involvement of focal adhesion kinase in the Fy … More n-signal transduction pathway was also demonstrated in the process of neocorticogenesis.2. Functional analysis of Fyn in the striatum: Fyn deficiency displays abnormal response to the administration of anti-psychotics such as haloperidol, a dopamine D2 receptor antagonist. In vivo and in vitro analysis revealed that haloperidol activates Fyn, and activated Fyn stimulates the tyrosine-phosphorylation of NMDA receptor NR2B subunit, subsequently enhancing the channel activity of NMDA receptor and the excitability of the striatal neurons.3. Functional analysis of Fyn in the amygdala: since abnormal response to NMDA administration is found in the amygdala of Fyn deficiency, comprehensive analysis on the difference of gene expression in the amygdala between the control and Fyn deficiency was carried out following NMDA administration. Based on the laser capture micro-dissection and cDNA array analysis revealed that Swim6 gene was significantly down regulated in the amygdalar central nucleus of Fyn deficiency. I t was suggested that Swim6 is functionally coupled to MAPK signal transduction pathway. Less