ERK2 Specific Function of the CNS

描述（由申请人提供）：ERK1和ERK2是进化保守的，从酵母到人类，普遍存在。这些蛋白的激活刺激转录和翻译，从而诱导必要的细胞代谢变化，这是CMS发育、功能和生存所必需的。然而，ERK1和ERK2缺失小鼠模型显示出截然不同的结果，其中ERK1消融没有明显的表型，而ERK2缺失的动物是胚胎致死的。因此，利用Cre/LoxP技术生成了ERK2基因的条件突变，以研究ERK2在CMS中的具体作用。由于有证据表明ERK1和ERK2在细胞周期转变事件、丝裂原激活的信号转导和突触可塑性中具有差异和特异性的活性，因此本研究的具体目的是确定CMS GFAP+细胞中ERK2的缺失如何破坏神经发育，ERK2的缺失如何影响培养的星形胶质细胞和神经元的细胞代谢活性，以及它如何影响学习和记忆。将利用转基因脑的体内检测和培养的星形胶质细胞和神经元的体外检测来确定ERK2的特异性功能。

DESCRIPTION (provided by applicant): ERK1 and ERK2 are evolutionary conserved from yeast to human, and are ubiquitous. The activation of these proteins stimulates transcription and translation which induce essential cellular metabolic changes required for proper CMS development, function, and survival. ERK1 and ERK2 null mouse models exhibit contrasting results however, where ERK1 ablation has no overt phenotype while ERK2 null animals are embryonic lethal. Therefore, a conditional mutation of the ERK2 gene using Cre/LoxP technology was generated to investigate the specific actions of ERK2 in the CMS. Because evidence suggests that ERK1 and ERK2 have differential and specific activities in cell cycle transition events, mitogen-activated signal transduction, and synaptic plasticity, the specific aims of this proposal are to determine how a loss of ERK2 in GFAP+ cells of the CMS disrupts neural development, how the loss effects the cellular metabolic activity of cultured astrocytes, and neurons, and how it effects learning and memory. Both in vivo examination of transgenic brains and in vitro examination of cultured astrocytes and neurons will be utilized for determination of ERK2 specific function.