NRAMP--MYCOBACTERIAL RESISTANCE, MRNA STABILITY AND IRON

描述 宿主对感染性物质的先天抵抗力在 确定由病原微生物感染是否进展到 疾病或微生物是否被消灭。对人类社会的抵抗 几种细胞内病原体的生长，包括分枝杆菌， 沙门氏菌和利什曼原虫由巨噬细胞介导，并受 一种基因，现在被称为Nramp1，一种与自然抵抗相关的巨噬细胞 蛋白。该基因似乎控制巨噬细胞的功能能力。 这样，表达功能蛋白的巨噬细胞似乎处于 比不表达的巨噬细胞更高的激活状态 一种功能性蛋白质。基因产物在控制中的作用 耐药性尚不清楚。根据核苷酸序列分析，推导出 蛋白质似乎是一种运输蛋白质。具体目标是：1) 使用肺和脾巨噬细胞的分枝杆菌耐药性与 Nramp1基因在Nramp1和Nramp1中的稳定表达 2)确定Nramp1Gly169在小鼠中的作用 过渡金属转运；3)确定细胞内铁和 Nramp1基因在转基因细胞系中的mRNA稳定性和蛋白质合成 Nramp1Gly169和Nramp1Asp169；4)确定mRNA的作用机制 铁诱导的稳定性。

DESCRIPTION Innate host resistance to infectious agents plays an important role in determining whether infection by pathogenic microorganisms progresses to disease or whether the microorganisms are eliminated. Resistance to the growth of several intracellular pathogens, including Mycobacteria, Salmonella and Leishmania is mediated by the macrophage and is controlled by a gene, now called Nramp1, a natural resistance associated macrophage protein. The gene appears to control the functional capacity of macrophages such that macrophages that express the functional protein appear to be at a more heightened state of activation than are macrophages that do not express a functional protein. The function of the gene product in controlling resistance is not known. Based on nucleotide sequence analysis the deduced protein appears to be a transport protein. The specific aims are to: 1) correlate mycobacterial resistance, using lung and splenic macrophages, with stable expression of mRNA and the intracellular iron with Nramp1 using both congenic and transgenic mice; 2) determine the role of Nramp1Gly169 in transition metal transport; 3) determine the role of intracellular iron and Nramp1 in mRNA stability and protein synthesis using cell lines transfected with Nramp1Gly169 and Nramp1Asp169; and 4) determine the mechanism of mRNA stability induced by iron.