CYSTEINE DIOXYGENASE TRANSGENIC MOUSE MODEL

半胱氨酸双加氧酶（CDO）活性异常或缺陷已被声称在患有与衰老相关的各种慢性疾病（非神经性和神经性）的个体中观察到。 低CDO活性可能导致病理学，因为硫酸盐或牛磺酸供应不足，半胱氨酸催化剂的产物，或因为半胱氨酸或有毒代谢物的积累。CDO基因多态性的证据已在人群中报道。 来自患有类风湿性关节炎、帕金森病、阿尔茨海默病、运动神经元病和其他疾病的患者的数据表明，低CDO活性可能与这些疾病的发生、严重程度或进展速度相关。我们的具体目标是：1. 目的：克隆小鼠COD基因，并对其进行鉴定. 2. 开发CDO活性低或缺失的CDO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）和个体易患某些退行性疾病的作用。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以及与尿牛磺酸和硫酸盐水平的关系，目的是确定允许研究人群中CDO活性变化的无创参数。 2. 探讨CDO活性与慢性退行性疾病的关系。

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.