MODIFICATION OF BRAIN SPECIFIC CYCLIN DEPENDENT KINASE GENES

脑特异性细胞周期蛋白依赖性激酶基因的修饰

• 批准号: 6111916
• 负责人: R O BRADY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6111916
• 关键词: cell cycle; cell growth regulation; cell line; cyclin dependent kinase; developmental neurobiology; enzyme activity; gene expression; gene mutation; gene targeting; laboratory mouse; neurochemistry; neurofilament; nucleic acid sequence; structural genes; tau proteins; thymidine kinase

The cdc5 family of protein kinases has a major role in the regulation of the cell cycle in eukaryotes. In order to determine the role of the cdk5 in brain development, we created cdk5 knock-out (-/-) mice. The life-span of these mice was greatly shortened. The brains of these mice lack cortical laminar structure and cerebellar foliation. Recent studies revealed that the Cdk5 (-/-) thalamic axons project through the cerebral cortex with abnormal trajectories and cortical plate neurons were inverted according to their birth date. The cells of the preplate were separated into subplate and marginal zone by neurons with the morphology of normal pyramidal neurons. Some of the axons of these cells projected correctly to the thalamic anlage. The results suggest that further cortical development is blocked in the Cdk5 (-/-) mice at an intermediate stage soon after the splitting of the preplate. Comparison with Cdk5 (-/-) with reeler and scrambler mice indicates that the cdk5 deficiency causes distinct pathological changes. The results suggest that Cdk5 participates in a separate, perhaps parallel, pathway of brain development.

蛋白激酶的cdc 5家族具有主要作用 在真核生物细胞周期的调控中起着重要作用。为了 为了确定cdk 5在大脑发育中的作用，我们创造了 CDK 5敲除（-/-）小鼠。这些老鼠的寿命大大缩短了 缩短这些老鼠的大脑缺乏皮层层状结构 和小脑叶。最近的研究表明，Cdk 5（-/-） 丘脑轴突穿过大脑皮层， 轨迹和皮质板神经元被倒置， 他们的出生日期将预平板的细胞分离成 亚板区和边缘区的神经元， 正常锥体神经元。这些细胞的一些轴突 正确地投射到丘脑原基。结果提示 在Cdk 5（-/-）小鼠中， 中间阶段后不久分裂的前板。 与Cdk 5（-/-）在reeler和scrambler小鼠中的比较 表明CDK 5缺乏引起明显的病理性 变化结果表明，Cdk 5参与了一个单独的， 也许是平行的大脑发育途径。