MODIFICATION OF BRAIN SPECIFIC CYCLIN DEPENDENT KINASE GENES

已知蛋白激酶的cdc 2家族的成员具有 在真核生物细胞周期调控中起关键作用。 的 神经元特异性cdc 2样激酶在稳定 在轴突形态发生中， 神经丝和tau的磷酸化没有被很好地描述。 的 该项目的主要目标是破坏 神经元CDC 2样激酶（CDK 5），并产生小鼠模型，以研究 这些激酶的功能;并在神经细胞中过表达CDK 5 线和在小鼠体内。 在过去的一年里，我们成功地 产生CDK 5敲除小鼠。 老鼠的寿命 Cdk 5（-/-）小鼠的大脑缺乏皮质层 结构和小脑叶。 脑干中的大型神经元 在脊髓中表现出染色质溶解性变化， 神经丝免疫反应性。 cdk 5似乎是一个重要的 脑发育和神经元分化的分子。 的 结果表明CDK 5在神经细胞骨架中具有重要作用 结构和组织。

Members of the cdc2 family of protein kinases are known to have a pivotal role in the regulation of cell cycle in eukaryotes. The potential roles of neuronal-specific cdc2-like kinase in stabilizing the neurofilament seketon and in axonal morphogenesis through phosphorylation of neurofilament and tau are not well delineated. The main objectives of this project are to disrupt the genomic locus of neuronal cdc2-like kinase (cdk5) and generate mouse models to study the function of these kinases; and to overexpress cdk5 in neuronal cell lines and in vivo in mice. During the past year, we have successfully generated cdk5 knock-out mice. The life-span of the mice is greatly shortened and the brains of the Cdk5(-/-) mice lack cortical laminar structure and cerebellar foliation. The large neurons in the brain stem and in the spinal cord show chromatolytic changes with accumulation of neurofilament immunoreactivity. Cdk5 appears to be an important molecule for brain development and neuronal differentiation. The results suggest that cdk5 has critical roles in neuronal cytoskeleton structure and organization.