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

硫酸盐是细胞生长和生存所必需的营养物质。尽管如此，临床很少测量硫酸盐水平，对血液硫酸盐水平紊乱的后果知之甚少。人体肾脏调节体内的硫酸盐水平，其机制尚未完全确定。我们的实验室已经从人类和小鼠身上分离出一个基因（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，尿液中流失的硫酸盐很少。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人血液中的硫酸盐含量降低。这些疾病中低血硫酸盐水平的机制尚未被确定。最近，我们培育了一只缺乏Nas1基因的小鼠。这只老鼠的血液硫酸盐含量很低，患有生长迟缓，生育能力下降和癫痫发作。在本研究中，我们计划在Nas1敲除小鼠中研究这些现象，并确定低血硫酸盐水平在这些情况中的作用。我们还计划利用基因阵列方法来描述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敲除小鼠中研究伤口修复和解毒过程，我们预计由于低血硫酸盐水平而受到影响。这些研究将确定硫酸盐在哺乳动物生理学中的作用，并将为研究与血液硫酸盐水平变化相关的疾病提供基础。

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.