CYSTEINE DIOXYGENASE TRANSGENIC MOUSE MODEL

半胱氨酸双加氧酶转基因小鼠模型

• 批准号: 6198521
• 负责人: MARTHA H STIPANUK
• 金额: $ 7.95万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6198521
• 关键词: aging; biological models; cysteine; enzyme activity; genetic polymorphism; genetic susceptibility; genetically modified animals; laboratory mouse; model design /development; molecular cloning; oxygenases

Abnormal or deficient cysteine dioxygenase (CDO) activity has been claimed to be seen in individuals with a variety of chronic diseases, both non-neurological and neurological, that are associated with aging. Low CDO activity may result in pathologies, either because of an insufficient supply of sulfate or taurine, products of cysteine catabolism, or because of accumulation of cysteine or toxic metabolites. Evidence for polymorphisms in the CDO gene has been reported in the human population. Data from patients with rheumatoid arthritis, Parkinson's disease, Alzheimer's disease, motor neuron disease, and other diseases, suggest that low CDO activity may be associated with the occurrence, severity, or speed of progression of these diseases. Our specific aims are: 1. To clone and characterize the murine COD gene. 2. To develop a CDO transgenic/knock-out mouse model of low or absent CDO activity for study of the role of variations in CDO activity on nutritional requirements (especially for cysteine, taurine and sulfate) and in predisposition of individuals to certain degenerative diseases. Our long term goals are: 1. To determine the relationship of tissue CDO activity to tissue and plasma cysteine, glutathione, sulfate and taurine levels and to urinary taurine and sulfate levels with the goal of identifying noninvasive parameters that would allow the study of variations CDO activity in human populations. 2. To study the relationship of CDO activity to chronic degenerative disease.

半胱氨酸双加氧酶(CDO)活性异常或缺乏，已被认为存在于与衰老相关的各种慢性疾病中，包括非神经系统疾病和神经系统疾病。CDO活性低可能导致病理，要么是由于半胱氨酸分解代谢产物硫酸盐或牛磺酸供应不足，要么是因为半胱氨酸或有毒代谢物的积累。已有证据表明CDO基因在人类群体中存在多态性。来自类风湿性关节炎、帕金森氏病、阿尔茨海默病、运动神经元病和其他疾病患者的数据表明，CDO活性低可能与这些疾病的发生、严重程度或进展速度有关。我们的具体目标是：1.克隆和鉴定小鼠COD基因。2.建立CDO活性低或缺失的转基因/基因敲除小鼠模型，用于研究CDO活性变化对营养需求(特别是半胱氨酸、牛磺酸和硫酸盐)的影响以及个体对某些退行性疾病的易感性。我们的长期目标是：1.确定组织CDO活性与组织和血浆半胱氨酸、谷胱甘肽、硫酸盐和牛磺酸水平的关系，以及与尿牛磺酸和硫酸盐水平的关系，目的是确定无创性参数，以便研究CDO活性在人类群体中的变化。2.探讨CDO活性与慢性退行性疾病的关系。