PRODUCTION AND MAINTENANCE OF H-2 MUTATIONS

该项目有两个基本目标。 一是进行决赛 筛选程序专门针对H-2突变的恢复， 可以回答有关涉及的过程的基本问题 在他们这一代。 二是继续满足其他方面的要求。 突变体的调查人员，并在项目期间， 逐步淘汰主动繁殖，最终保存 冷冻胚胎库中的突变体 大多数（如果不是全部的话）体内H-2突变具有 已经被解释为意味着它们的产生是通过一个过程， 非等位基因之间的DNA序列转移（微重组 或“基因转换”，而不是简单地依赖于单一的 基地变化。 其中一个基本的信息缺失， 这种过程的建模/测试是这种转移是否可以 明确归因于顺式（单染色体内）或反式 （同源染色体之间）构型。 该项目提出了一个 有限和定向筛选计划，以试图识别H-2 可以明确归因于顺式或反式基因的突变 转换”。 这样的搜索不太可能发生在其他地方。 实际 演示这些事件将有助于分析这一过程 许多人认为其在体内产生 MHC的多样性。 这个项目还建议继续维持一个鼠群 携带H-2组织相容性基因突变作为资源集落。 新 如果突变体可用，可以添加它们。 保持菌株 将通过皮肤移植进行系统监测，以确保其遗传 完整 目前的请求频率表明， 繁殖群体仍然有理由尽快满足要求。 然而，随着繁殖地的逐渐消失， 计划建立胚胎库，以容纳P.I.的未来计划。

This project has two basic objectives. The first is to conduct a final screening program specifically aimed at the recovery of H-2 mutations which can answer basic questions about the process(es) which have been implicated in their generation. The second is to continue meeting requests from other investigators for mutants and, over the course of the project period, to phase out the active breeding and culminate with the preservation of the mutants in a frozen embryo bank. Most, if not all, of the in vivo H-2 mutations have characteristics which have been interpreted to imply their generation via a process involving transfers of DNA sequences between non-allelic genes (micro-recombination or "gene conversion" rather than relying on simply the accretion of single base changes. One of the basic pieces of information missing for the modeling/testing of such a process is whether such transfers can definitively be attributed to cis-(within-single chromosomes) or trans (between homologous chromosomes) configurations. This project proposes a limited and directed screening program to attempt to identify H-2 mutation-s which can definitively be attributed to cis or to trans "gene conversions". Such an search is unlikely to occur elsewhere. Actual demonstration of such events will facilitate the analysis of this process which is thought by many to be important in the in vivo generation of diversity within the MHC. This project also proposes to continue the maintenance of a colony of mice bearing H-2 histocompatibility gene mutations as a resource colony. New mutants may be added, if and as they become available. Maintained strains will be systematically monitored by skin grafting to ensure their genetic integrity. The current frequency of requests suggests that an actively breeding colony is still justifiable to expeditiously fulfill the requests. However the phasing out of the breeding colony, and its entry into a frozen embryo bank(s), is planned in order to accommodate the P.I.'s future plans.