A Drosophila mutant for MnSOD:its functional role in development and tissue aging

果蝇 MnSOD 突变体：其在发育和组织衰老中的功能作用

• 批准号: 7152329
• 负责人: AMY BELTON
• 金额: $ 5.29万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7152329
• 关键词: Drosophilidae; aging; antioxidants; arthropod genetics; biological models; cellular pathology; enzyme activity; free radical oxygen; gene deletion mutation; invertebrate embryology; longevity; manganese; mitochondria; molecular genetics; oxidative stress; predoctoral investigator; sex linked trait; superoxide dismutase; tissues

DESCRIPTION (provided by applicant): The free radical theory of aging typifies aging as an outcome of indiscriminate, random, and cumulative damage to different cellular components caused by reactive oxygen species (ROS). Mitochondrial protection from free radical damage as offered by the enzyme Manganese superoxide dismutase (MnSOD) is indispensable, since mitochondria handle the bulk of intracellular oxygen, the long-term goal of this study is to elucidate the role of MnSOD activity in aging and tissue degeneration thereof. The fruitfly Drosophila melanogaster deploys a defense system to fight against ROS that is very similar to that of humans and previous studies of aging in Drosophila have indicated the importance of antioxidant enzymes in maximum life span extension. The foremost objective of this dissertation work was to obtain a complete loss of function mutation for MnSOD gene in Drosophila. As expected, a complete loss of MnSOD function confers severely reduced lifespan leading to neonatal lethality in Drosophila, same in mouse. This MnSOD mutant model will now enable me to (1) investigate the effect of anti-oxidant activity during development because the severity of the homozygote phenotype seen-death within 24 hours clearly suggest residual effect from development; (2) investigate the effect of loss of MnSOD function in specific tissue or cell types, testing the hypothesis that loss of MnSOD function is associated with increased oxidative stress causing accelerated tissue damages. Thus, with the help of some unique moleculargenetic tools available in Drosophila, my Ph.D dissertation work will enable me to answer several previously unanswered questions related to the biology of aging process.

描述（由申请人提供）：衰老的自由基理论代表衰老是对由活性氧（ROS）引起的不同细胞成分的不分毒，随机和累积损害的结果。线粒体保护酶锰超氧化物歧化酶（MNSOD）提供的自由基损伤是必不可少的，因为线粒体处理了大部分细胞内氧，因此这项研究的长期目标是阐明MNSOD活性在Aging and Tissue Demenation Wenof中的作用。果蝇果蝇Melanogaster部署了一种防御系统来与ROS作斗争，与人类非常相似，并且先前对果蝇衰老的研究表明，抗氧化酶在最大寿命延长中的重要性。这项论文工作的最重要目标是获得果蝇中MNSOD基因的功能突变的完全丧失。正如预期的那样，MNSOD功能的完全丧失赋予了寿命严重降低，导致果蝇的新生儿致死性，在小鼠中相同。现在，该MNSOD突变体模型将使我能够（1）研究发育过程中抗氧化活性的作用，因为在24小时内纯合子表型的严重程度清楚地表明发育中的残留效应； （2）研究了MNSOD功能在特定组织或细胞类型中的丧失的影响，检验了以下假设：MNSOD功能的丧失与氧化应激增加有关，从而导致加速组织损伤。因此，借助果蝇中提供的一些独特的分子工具，我的博士学位论文工作将使我能够回答与衰老过程生物学有关的几个以前未解决的问题。