Genetic Analysis of the Role of Pro-opiomelanocortin Peptides in Mouse Adrenal Maintenance and Function

前阿黑皮素（POMC）是脊椎动物中高度保守的基因。它编码一种激素原，由其产生许多具有多种功能的小肽，包括促肾上腺皮质激素、促黑素细胞激素和β-内啡肽。研究人员产生了完全缺乏所有POMC肽的小鼠突变体。虽然POMC无效突变体出生时具有形态正常的肾上腺，但它们的肾上腺表现出两个缺陷：第一，它们不释放糖皮质激素，并且它们产生的盐皮质激素水平降低;第二，它们随着年龄的增长而退化，最终在成人中缺乏。在本项目中，研究人员将利用他们的小鼠模型在一个完整的动物，结合药理学和遗传学的方法a），以确定特定的POMC肽或肽组合所需的维持和功能的肾上腺，和B），以确定在肾上腺介导的分子过程，其维持和功能，是依赖于POMC衍生的信号。该项目将通过推进发现和理解来整合研究和教育，同时在概念上和实践上培训不同层次的学生。拟议的研究将扩大代表性不足的群体的参与，特别是在俄克拉荷马州的地理代表性不足的群体。拟议的研究对科学的好处在于阐明脊椎动物器官维持和功能的一般原则，这些教训将适用于许多其他生物系统。建议的研究对社会的好处在于促进知识和促进教育。

Pro-opiomelanocortin (POMC) is a gene highly conserved in vertebrates. It encodes for a pro-hormone from which a number of small peptides with a diverse array of functions is produced, including adrenocorticotropin, melanocyte stimulating hormone, and -endorphin. The investigators generated a mouse mutant which completely lacks all POMC peptides. While POMC null mutants are born with morphologically normal adrenal glands, their adrenals exhibit two defects: First, they do not release glucocorticoids, and they produce reduced levels of mineralocorticoids; and second, they regress with age and are eventually lacking in the adult. In this project the investigators will utilize their mouse model in a whole animal, combined pharmacological and genetic approach a) to identify the specific POMC peptide or peptide combination required for maintenance and function of the adrenals, and b) to identify the molecular processes in the adrenal mediating its maintenance and function that are dependent on POMC-derived signals. This project will integrate research and education by advancing discovery and understanding while at the same time training, both conceptually and practically, students at different levels in their scientific careers. The proposed research will broaden the participation of underrepresented groups, specifically of geographically underrepresented groups in the State of Oklahoma. The benefit of the proposed research to science lies in illuminating general principles of organ maintenance and function in vertebrate organisms, lessons which will be applicable to many other biological systems. The benefit of the proposed research to society lies in advancing knowledge and promoting education.