ZINC TRANSPORTER FUNCTIONS IN MICE

描述：该项目建议使用遗传技术来获得 更好地了解小鼠的锌代谢。 基因家族 编码跨膜蛋白，其促进锌从 细胞质被克隆了。 该家族包括ZnT-1，其转运 锌的细胞; ZnT-2，这有利于锌的积累， 内体/溶酶体区室，和ZnT-3，其通过同源性克隆至 ZnT-2在神经元细胞中表达，其在突触中螯合锌。 囊泡 这些基因可能在保护细胞免受 过量的锌和/或促进细胞内锌的浓度 它可以提供特殊功能的隔间。 测试这些 假设，这些转运蛋白的表达将被分析，在两个 组织和细胞水平，这些信息将用于帮助 解释这些基因失活的小鼠的表型 通过同源重组。 缺乏锌转运蛋白和 金属硫蛋白也将产生，以帮助确定这些作用， 金属结合蛋白 这些实验最令人兴奋的结果可能是 证明锌具有重要的神经调节功能。

DESCRIPTION: This project proposes to use genetic techniques to gain a better understanding of zinc metabolism in the mouse. A family of genes encoding transmembrane proteins that facilitate removal of zinc from the cytoplasm has been cloned. This family includes ZnT-1, which transports zinc out of the cell; ZnT-2, which facilitates accumulation of zinc in endosomal/lysosomal compartments, and ZnT-3, which was cloned by homology to ZnT-2 and is expressed in neuronal cells that sequester zinc in synaptic vesicles. These genes may play an essential role in protecting cells from excess zinc and/or facilitating the concentration of zinc in intracellular compartments where it may serve special functions. To test these hypotheses, the expression of these transporters will be analyzed, at both the tissue and cellular level, and that information will be used to help interpret the phenotypes of mice in which each of these genes is inactivated by homologous recombination. Mice lacking both zinc transporters and metallothioneins will also be generated to help define the role of these metal-binding proteins. The most exciting outcome of these experiments may be the demonstration that zinc has important neuromodulator functions.