CORTICOTROPIN RELEASING HORMONE BINDING PROTEIN

促肾上腺皮质激素释放激素结合蛋白

• 批准号: 6340146
• 负责人: AUDREY F. SEASHOLTZ
• 金额: $ 8.65万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-12-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6340146
• 关键词: DNA binding protein; DNA footprinting; animal tissue; cell type; corticosteroid receptors; corticotropin releasing factor; cyclic AMP; dexamethasone; fusion gene; gel electrophoresis; gene expression; genetic library; genetic mapping; genetic regulation; genetic regulatory element; genetic transcription; glucocorticoids; hormone regulation /control mechanism; human tissue; laboratory rat; neoplastic cell culture for noncancer research; nucleic acid sequence; protein purification; reporter genes; site directed mutagenesis; tissue /cell culture; transcription factor; transfection

DESCRIPTION (Adapted from the applicant's abstract): In light of the ability of CRH-BP to antagonize the biological activity of CRH in vitro, it is hypothesized that the CRH-BP modulates the actions of CRH in the pituitary and central nervous system. This hypothesis is tested by several independent approaches presented in this proposal. First, in situ hybridization histochemistry, immunocytochemistry, and RNase protection assays will be utilized to characterize the in vivo regulation of CRH-BP expression within the HPA axis during development and in response to glucocorticoids and stress, two important modulators of CRH expression and HPA activity. The expression and regulation of CRH-BP will also be examined in CRH-deficient mice. Second, the physiological consequences of increased level of CRH-BP in the anterior pituitary will be assessed in a transgenic mouse model of anterior pituitary CRH-BP overexpression. Third, the physiological consequences of decreased CRH-BP levels will be determined in a mammalian model of CRH-BP deficiency created by targeted mutation of the CRH-BP gene in embryonic stem cells. Together, these studies should allow the investigators to elucidate the physiological role of the CRH-BP in pituitary and brain. Finally, studies on the molecular characterization of CRH-BP gene regulation will be initiated in a number of CRH-BP expressing cell lines.

描述（改编自申请人摘要）：鉴于