ERK2 Specific Function of the CNS

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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.