X-LINKED MINOR HISTOCOMPATIBILITY BARRIERS IN MICE

小鼠中 X 连锁的次要组织相容性障碍

• 批准号: 6312073
• 负责人: THOMAS R KING
• 金额: $ 13.68万
• 依托单位: CENTRAL CONNECTICUT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6312073
• 关键词: alleles; animal genetic material tag; gene expression; genetic strain; histocompatibility antigens; homologous transplantation; immunogenetics; laboratory mouse; linkage mapping; minor histocompatibility loci; molecular genetics; sex chromosomes; transplantation immunology

DESCRIPTION (Applicant's Abstract): This proposal is focused on the whole-animal and molecular characterization of X-linked minor histocompatibility (H) barriers in mice. One such allogenic locus on the X, dubbed H-Xby Bailey and more recently renamed Hxa, has been described previously for 4 different inbred mouse strain combinations, but has not been characterized in any detail. Here we propose to reopen investigation of X-linked minor histocompatibility barriers in mice, with the principle aim of integrating this classical whole-animal immunogenetic phenotype (allograft rejection) with the recently established molecular genetic framework of the murine X chromosome. In general, we aim to further characterize the X-linked minor H barriers we identify between various inbred strain combinations by mapping each antigenic locus to one or more discrete locations on the mouse X chromosome. This approach will also allow us to test two current hypotheses in immunogenetics. First, fine structure mapping of the gene(s) responsible for X-linked histoincompatibility will allow us to test the two-gene model for minor histocompatibility-locus structure recently proposed by Roopenian and coworkers. X-linked histoincompatibility will provide a unique test of this model, as the proposed components of this classical H locus could be widely spread apart on the X chromosome, rather than tightly linked as has been found for all the autosomal H-loci studied. Second, by taking this mapping approach independently with several different inbred strain combinations we will be able to test the hypothesis that the various examples of X-linked histoincompatibility in mice identify different alleles of a single Hxa locus. Instead, it could be that each different X-mediated interstrain histoincompatibility could identify distinct sets of antigen-encoding loci of importance in transplantation biology. Whatever the outcome in terms of Hxa structure and allelism, the approach we describe will set the stage for the eventual positional cloning of any X-linked histocompatibility locus we identify.

描述（申请人的摘要）：本提案集中于 X连锁次要染色体的整体动物和分子表征 组织相容性（H）屏障。X染色体上的一个这样的同种异体基因座， 被贝利命名为H-X，最近更名为Hxa， 以前用于4种不同的近交系小鼠品系组合，但尚未 以任何细节为特征的。 在这里，我们建议重新调查的X连锁次要组织相容性 屏障，其主要目的是整合这种经典的 全动物免疫遗传表型（同种异体移植排斥反应）与最近的 建立了小鼠X染色体的分子遗传框架。总的来说， 我们的目标是进一步描述我们发现的X连锁小H障碍， 通过将每个抗原基因座定位到 小鼠X染色体上的一个或多个离散位置。这种方法将 这也让我们能够检验免疫遗传学中的两个现有假设。第一，好 X连锁组织不相容性基因的结构定位 将使我们能够测试两个基因模型的次要组织相容性位点， Roopenian及其同事最近提出的结构。x连锁 组织不相容性将提供一个独特的测试这个模型，因为建议 这个经典的H基因座的组成部分可以在X染色体上广泛分布， 染色体，而不是紧密相连，因为已经发现所有的常染色体 研究了H位点。其次，通过独立地采用这种映射方法， 几种不同的近交系组合，我们将能够测试 假设小鼠中的各种X连锁组织不相容性的例子 鉴定单个Hxa基因座不同等位基因。相反，它可能是 每种不同的X介导的株间组织不相容性都可以鉴定 在移植中重要的不同的抗原编码基因座组 生物学无论Hxa结构和等位性的结果如何， 我们描述的方法将为最终的定位克隆奠定基础。 任何X染色体连锁的组织相容性位点

项目成果

An X-encoded alloantigenicity between BALB/c and C57BL/6 strains of mice.

BALB/c 和 C57BL/6 品系小鼠之间的 X 编码同种异体抗原性。

• DOI: 10.1007/s00251-003-0554-0
• 发表时间: 2003
• 期刊: Immunogenetics
• 影响因子: 3.2
• 作者: Alner,Kadie-Ann;Loman,Jeannette;Hall,EmilyH;Mutcherson2nd,RayeJ;King,ThomasR
• 通讯作者: King,ThomasR