ERK2 Specific Function of the CNS

描述（由申请人提供）：ERK 1和ERK 2从酵母到人是进化保守的，并且是普遍存在的。这些蛋白质的激活刺激转录和翻译，从而诱导适当CMS发育、功能和存活所需的基本细胞代谢变化。然而，ERK 1和ERK 2缺失小鼠模型表现出相反的结果，其中ERK 1消融没有明显的表型，而ERK 2缺失动物是胚胎致死的。因此，使用Cre/LoxP技术产生ERK 2基因的条件突变以研究ERK 2在CMS中的特异性作用。因为有证据表明，ERK 1和ERK 2在细胞周期转换事件，有丝分裂原激活的信号转导和突触可塑性中具有不同的和特定的活性，所以本提案的具体目的是确定CMS的GFAP+细胞中ERK 2的丢失如何破坏神经发育，丢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。转基因脑的体内检查和培养的星形胶质细胞和神经元的体外检查都将用于测定ERK 2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.