HOMEOPROTEIN AND NEUROENDOCRINE PHENOTYPE

同源蛋白和神经内分泌表型

• 批准号: 2416360
• 负责人: Elaine J. Lewis
• 金额: $ 18.38万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2416360
• 关键词: catecholamines; developmental genetics; developmental neurobiology; dopamine beta monooxygenase; enzyme induction /repression; hormone biosynthesis; laboratory mouse; laboratory rat; neuroendocrine system; neurotransmitter biosynthesis; norepinephrine; nucleic acid sequence; oligonucleotides; phenotype; transcription factor

DESCRIPTION: One of the key events defining the specificity of cell function in neuroendocrine tissues is the identity of neurotransmitter expressed in a given cell. The molecular events that control the selection of neurotransmitter phenotype are influenced by environmental stimuli. Ultimately, cellular phenotype is determined by the interaction of functionally distinct transcription factors with regulatory elements of genes that encode neurotransmitters or neurotransmitter biosynthetic enzymes. This application is focused on characterizing a transcription factor that interacts with the regulatory region of the dopamine b hydroxylase (DBH) gene. DBH catalyzes the synthesis of norepinephrine, and is expressed only in sympathetic neurons, adrenal chromaffin cells and certain brain nuclei. The applicant has cloned a cDNA for this transcription factor, designated Arix, which carries a homeobox, and has found that Arix mRNA is selectively expressed in noradrenergic tissues and cell lines. These observations suggest that Arix may play a definitive role in the determination of the noradrenergic phenotype in vivo. The main objective of this proposal is to understand the potential role of Arix in regulating the noradrenergic phenotype. This goal will be achieved by: (1) defining the pattern of Arix expression in the rat peripheral and central nervous system during embryonic and postnatal development; (2) identifying the molecular components of Arix-containing DNA-protein complexes, and (3) inactivating Arix activity in a catecholaminergic cell line. The results of these studies should lead to further understanding of the normal development of the sympathoadrenal phenotype, as well as the consequences of a failure of development to proceed. In addition, the Arix gene may prove to be a factor in inherited diseases characterized by the aberrant development of neuroendocrine cells.

描述：定义细胞特异性的关键事件之一 神经内分泌组织的功能是神经递质的身份 在给定的细胞中表达。这些控制着 神经递质表型的选择受环境的影响 刺激。最终，细胞表型由相互作用决定 具有调节元件的功能不同的转录因子 编码神经递质或神经递质生物合成的基因 内切酶该应用程序的重点是表征转录 与多巴胺B调节区相互作用的因子 羟化酶（DBH）基因。DBH催化去甲肾上腺素的合成， 并且仅在交感神经元、肾上腺嗜铬细胞 和某些脑核团申请人已经为此克隆了cDNA。 转录因子，命名为Arix，携带同源框，并具有 发现Arix mRNA选择性地在去甲肾上腺素能组织中表达 和细胞系。这些观察表明，Arix可能扮演一个 在确定去甲肾上腺素能表型中的决定性作用 vivo.本提案的主要目的是了解 Arix在调节去甲肾上腺素能表型中的作用。这一目标将 通过以下方式实现：（1）确定大鼠中Arix表达的模式， 胚胎期和出生后的外周和中枢神经系统 开发;（2）鉴定含Arix的分子组分 DNA-蛋白质复合物，和（3）在一个 儿茶酚胺能细胞系这些研究的结果应该会导致 进一步了解交感肾上腺的正常发育 表型，以及发展失败的后果， 继续. 此外，Arix基因可能是一个因素， 以异常发育为特征的遗传病 神经内分泌细胞