PRODUCTION AND MAINTENANCE OF H-2 MUTATIONS

这个项目有两个基本目标。第一个是进行决赛 专门针对恢复H-2突变的筛查计划 可以回答有关被牵连的流程的基本问题 在他们这一代人中。第二是继续满足其他人的请求 变种人的调查人员，并在项目期间， 逐步淘汰活跃的繁殖，并以保护 冷冻胚胎库里的变种人。 体内的H-2突变中的大多数，如果不是全部的话，都具有 都被解释为通过一种涉及到 DNA序列在非等位基因之间的转移(微重组 或者“基因转化”，而不是简单地依赖于单个 基数变化。缺少的基本信息之一是 对这样一个过程的建模/测试是这样的传输是否可以 明确地归因于顺式(在单个染色体内)或反式 (在同源染色体之间)构型。该项目提出了一种 有限和定向的筛查计划，试图识别H-2 突变-S，可明确归因于顺式或反式基因 这样的搜索不太可能在其他地方发生。实际 这些事件的演示将有助于对这一过程的分析 这被许多人认为在体内的一代是重要的 MHC内部的多样性。 该项目还提议继续维持一群老鼠 携带H-2组织相容性基因突变的菌落作为资源菌落。新的 如果突变株可用，可能会添加它们。保持株系 将通过皮肤移植进行系统监测，以确保他们的基因 正直。目前的请求频率表明，一个积极的 繁殖群体仍有理由迅速满足要求。 然而，繁殖群体的逐步退出，以及它进入冻结的 胚胎库(S)，是为了适应P.I.‘S的未来计划而规划的。

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.