FISH MODEL FOR THE STUDY OF HEPATIC COPPER METABOLISM

该研究计划的总体目标是开发一种鱼类模型 对肝脏铜代谢的研究，以促进我们的 了解真核细胞中铜的分子动力学。 铜是一种剧毒金属，在其正常代谢过程中会发生变化 导致严重的细胞功能障碍，如在威尔逊病中表达的 疾病。白鲈鱼(Morone Americana)积聚得异常之高 肝脏中的铜含量(大于1000微克/克湿重) 在自然暴露的条件下。这些水平大大超过了 在肝豆状核变性患者中观察到的肝脏铜浓度。一个 与之关系密切的鱼类--条纹鱼(Morone Saxatilis) 肝脏铜水平与哺乳动物相似，并将作为对照。这个 这个项目的具体目标是确定哪些机制可以解释 因为白鱼体内铜的异常堆积。实验 利用分离的肝细胞和纯化的膜制剂进行研究 这两种鱼将研究膜运输和 铜蓄积过程中的胞内蛋白结合。的一个独特功能 这项研究表明，这两种鱼可以杂交产生杂交品种。 这将使我们能够研究积聚的基因控制 各种因素。预计这一鱼类模型将贡献新的知识 关于控制真核细胞中铜的动力学的机制。

The overall objective of this research program is to develop a fish model for the investigation of hepatic copper metabolism in order to advance our understanding of the molecular kinetics of copper in eukaryotic cells. Copper is a highly toxic metal and alterations in its normal metabolism result in severe cellular dysfunction, such as expressed in Wilson's disease. The white perch (Morone americana) accumulates exceptionally high copper concentrations in the liver (greater than 1000 Mug/g wet weight) under conditions of natural exposure. These levels are greatly in excess of hepatic copper concentrations observed in Wilson's disease patients. A closely related fish species, the striped bass (Morone saxatilis), exhibits hepatic copper levels similar to mammals and will serve as controls. The specific aim of this project is to determine the mechanisms which account for the abnormal accumulation of copper in white perch. Experimental studies using isolated hepatocytes and purified membrane preparations from these two fish species will investigate the role of membrane transport and intracellular protein binding in copper accumulation. A unique feature of this study is that the two fish species can be crossbred to produce hybrids which will allow us to investigate the genetic control of the accumulation factors. It is expected that this fish model will contribute new knowledge concerning the mechanisms which control copper kinetics in eukaryotic cells.