DEVELOPMENTAL IMMUNOGENETICS OF THE ZEBRAFISH BRADYDANIO RERIO

这个项目的目的是确定基因是至关重要的， 动物物种的免疫反应，允许仔细研究两者 发育生物学和进化遗传学。 目标是 不仅要了解免疫系统的功能，还要了解它是如何 以及它如何在进化中达到目前的水平 复杂程度。 斑马鱼Brachydanio rerio是一种有机体 代表了至少两亿年前的进化点 可以在实验室里廉价种植，是一个物种， 在可见的透明胚胎中的发育阶段， 在其基因组中有大量的遗传标记， 鉴定 我们已经开始了我们的努力，通过识别斑马鱼的基因， 显然与哺乳动物的结构相似：我们克隆了MHC I类基因、β 2-微球蛋白和免疫球蛋白恒定区 基因. 我们还确定了与下列项相关的不变链： 抗原加工，Ii. 目前正在尝试评估是否有任何 许多候选基因确实是T细胞受体， β 2-微球蛋白和不变链基因的表达使得 我们开始检查这些分子的功能守恒 在数百万年的时间里。 我们希望正在进行的关于组装的研究 斑马鱼β 2-微球蛋白与小鼠MHC I类，以及 斑马鱼不变链的功能及其组装研究 与MHC II类分子，将提供洞察一般 多聚体蛋白如何共同进化的问题。 这些研究也可以 帮助识别对装配重要的结构特征 和多聚体蛋白的稳定化。

This project is directed at identifying genes that are critical to the immune response in an animal species that allows careful study of both developmental biology and of evolutionary genetics. The goal is to understand not only how the immune system functions, but also how it developmentally arises and how in evolution it arrived at its current level of complexity. The zebrafish, Brachydanio rerio, is an organism that represents a point of evolution of at least 200 million years ago, can be grown cheaply in laboratories, is a species that undergoes its developmental stages in a visible transparent embryo, and for which a large number of genetic markers throughout its genome have been identified. We have begun our efforts by identifying genes of the zebrafish that clearly have similar structure to those of mammals: we have cloned MHC class I genes, beta2-microglobulin, and immunoglobulin constant region genes. We have also identified the invariant chain associated with antigen processing, Ii. Attempts are underway to evaluate whether any of a number of candidate genes are indeed T cell receptors, and protein expression of beta2-microglobulin and invariant chain genes has allowed us to begin to examine the conservation of function of these molecules over millions of years. We expect that studies underway on the assembly of zebrafish beta2-microglobulin with mouse MHC class I, as well as studies on the function of zebrafish invariant chain and its assembly with MHC class II molecules, will provide insight into the general question of how multimeric proteins coevolve. Such studies can also help to identify structural features that are important for the assembly and stabilization of multimeric proteins in general.