ERK2 Specific Function of the CNS

描述(申请人提供)：ERK1和ERK2是从酵母到人类进化保守的，普遍存在。这些蛋白的激活刺激转录和翻译，从而诱导CMS正常发育、功能和生存所需的必要的细胞代谢变化。然而，ERK1和ERK2缺失的小鼠模型显示出相反的结果，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，我们利用Cre/loxP技术对ERK2基因进行条件性突变，以研究ERK2基因在细胞质雄性不育中的特异性作用。由于有证据表明ERK1和ERK2在细胞周期转换事件、丝裂原激活的信号转导和突触可塑性中具有不同和特定的活性，本研究的具体目的是确定CMS的GFAP细胞中ERK2的缺失如何扰乱神经发育，如何影响培养的星形胶质细胞和神经元的细胞代谢活动，以及它如何影响学习和记忆。转基因大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都将用于确定ERK2的特定功能。

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.