Phenotypic studies of the NaSi-1 transporter knock-out mouse

NaSi-1转运蛋白敲除小鼠的表型研究

• 批准号: nhmrc : 401687
• 负责人: Prof Daniel Markovich
• 金额: $ 17.89万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/phenotypic-studies-nasi-out-mouse/98364
• 关键词: Phenotypic; studies; NaSi; transporter; knock

Sulfate is an essential nutrient for cell growth and survival. Despite this, sulfate levels are rarely measured clinically and very little is known about the consequences of disturbed blood sulfate levels.The human kidneys regulate sulfate levels in the body, by mechanisms that are not fully characterised. Our laboratory has isolated a gene (Nas1) from humans and mice, which encodes a protein involved in sulfate absorption from the diet. Nas1 also controls sulfate excretion into the urine, by regulating kidney reabsorption. Normally, very little sulfate is lost in the urine. However, individuals with autism, Alzheimers, Parkinsons, motor neurone disease and liver cirrhosis, have been reported to have reduced blood sulfate levels. The mechanisms underlying the low blood sulfate levels in these disorders, have not been characterised. Recently, we generated a mouse lacking the Nas1 gene. This mouse has very low blood sulfate levels and suffers from growth retardation, reduced fertility and displays seizures. In this study, we plan to investigate these phenomena in the Nas1 knock out mouse and determine the role of low blood sulfate levels on these conditions. We also plan to characterise the role of low blood sulfate levels on the expression of genes in various body organs, using a gene array approach. In addition, we plan to study wound repair and the detoxification process in our Nas1 knock out mouse, which we expect to be affected due to low blood sulfate levels. These studies will establish the roles sulfate plays in mammalian physiology and will provide a foundation for studying diseases that are associated with changes in blood sulfate levels.

硫酸盐是细胞生长和存活的必需营养素。尽管如此，硫酸盐水平在临床上很少被测量，并且对血液硫酸盐水平紊乱的后果知之甚少。人体肾脏通过尚未完全表征的机制调节体内硫酸盐水平。我们的实验室已经从人类和小鼠中分离出一种基因（Nas1），该基因编码一种参与饮食中硫酸盐吸收的蛋白质。Nas1还通过调节肾脏重吸收来控制硫酸盐排泄到尿液中。正常情况下，尿液中的硫酸盐损失很少。然而，据报道，患有自闭症、阿尔茨海默氏症、帕金森氏症、运动神经元疾病和肝硬化的个体血液硫酸盐水平降低。这些疾病中低血硫酸盐水平的潜在机制尚未得到表征。最近，我们培育了一只缺乏Nas1基因的小鼠。这只小鼠的血液硫酸盐水平非常低，患有生长迟缓、生育能力降低和癫痫发作。在这项研究中，我们计划在Nas1基因敲除小鼠中研究这些现象，并确定低血硫酸盐水平在这些条件下的作用。我们还计划使用基因阵列方法来验证低血硫酸盐水平对各种身体器官中基因表达的作用。此外，我们计划在我们的Nas1基因敲除小鼠中研究伤口修复和解毒过程，我们预计这将受到低血硫酸盐水平的影响。这些研究将建立硫酸盐在哺乳动物生理学中的作用，并为研究与血液硫酸盐水平变化相关的疾病提供基础。