Two unusual minor histocompatibility models in mice

小鼠中两种不寻常的次要组织相容性模型

• 批准号: 6802601
• 负责人: THOMAS R KING
• 金额: $ 20.21万
• 依托单位: CENTRAL CONNECTICUT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6802601
• 关键词: functional /structural genomics; gene mutation; genetic mapping; histocompatibility antigens; homologous transplantation; laboratory mouse; sex chromosomes; skin transplantation

DESCRIPTION (provided by applicant): These investigations promise to enhance research activity at CCSU by providing students with a variety of defined projects focused on the further characterization of two unusual minor histocompatibility (H) models in mice: H-hix and H.mshi. H-hix. for histoincompatibilitv on the X chromosome. Classical analysis of X-linked minor transplantation barriers has suggested that a single, polymorphic gene (Hxa) is responsible for generating skin-graft incompatibility among different inbred strains of mice. Our recent efforts to further characterize the X-linked incompatibility previously described for strains C57BL/6 and BALB/c has shown instead that this allograft rejection is mediated by at least two distinct antigens that are likely the products of more than one gene. Thus, we propose that these two strains encode different haplotypes of antigen-encoding loci (called H-hixb and H-hixC), rather than different alleles of a single Hxa locus. Furthermore, we hypothesize that other strain combinations may identity additional, distinct sets of X-linked antigen-encoding loci. Here we propose to genetically map the H-hixb, H-hixc disparity--as well as other H-hix haplotype pairs that we aim to identity--to test two current models regarding minor histocompatibility locus structure, and to provide a foundation for the future cloning and molecular analysis of each distinct H-hix component. H-mshi for histoincompatibility associated with the mshi mutation. The male sterility and histoincompatibility mutation (mshi) was initially detected on a BALB/c genetic background as a spontaneous antigen-loss type H variant that rejected wild-type skin grafts. Our previous work with this variant has shown that H-mshi may exemplify a new type of minor histocompatibility locus that has resulted from the mutation of a single, highly conserved gene; and mediates an unusual, cytotoxic-T-lymphocyte-independent rejection mechanism. In addition, we have genetically mapped mshi to a small region that includes fewer than 20 genes. Here we propose to screen these candidates to identify the gene disrupted by the mshi mutation. To confirm this molecular assignment and to allow the complete functional and structural dissection of H-mshi, we also propose to isolate a T-helper cell clone and serum antibodies specifically reactive to the H-mshi+ antigens.

描述（由申请人提供）：这些调查有望通过为学生提供各种定义的项目来加强CCSU的研究活动，这些项目专注于进一步表征小鼠中两种不寻常的次要组织相容性（H）模型：H-hix和H. mshi。 嗨X染色体上的组织不相容性。经典的分析表明，一个单一的，多态性基因（Hxa）是负责产生不同的近交系小鼠之间的皮肤移植不相容性的X连锁的小移植障碍。我们最近的努力，以进一步表征先前描述的菌株C57 BL/6和BALB/c的X-连锁不相容性，而不是表明，这种同种异体移植排斥反应是由至少两个不同的抗原，可能是一个以上的基因的产物介导的。因此，我们认为这两个菌株编码不同的抗原编码基因座单倍型（称为H-hixb和H-hixC），而不是一个单一的Hxa基因座的不同等位基因。此外，我们假设，其他菌株组合可能会识别额外的，不同的X连锁抗原编码基因座。在这里，我们建议遗传映射的H-hixb，H-hixc的差距-以及其他H-hix单倍型对，我们的目标是身份-测试两个目前的模型关于轻微的组织相容性位点结构，并提供一个基础，为未来的克隆和分子分析的每个不同的H-hix组件。 与mshi突变相关的组织不相容性。雄性不育和组织不相容性突变（mshi）最初检测到的BALB/c遗传背景作为一个自发的抗原丢失H型变异，拒绝野生型皮肤移植。我们以前的工作与这种变体表明，H-mshi可能是一种新类型的轻微的组织相容性位点，导致一个单一的，高度保守的基因突变，并介导一个不寻常的，细胞毒性T淋巴细胞独立的排斥机制。此外，我们已经将mshi基因定位到一个包含少于20个基因的小区域。在这里，我们建议筛选这些候选人，以确定被mshi突变破坏的基因。为了确认这种分子分配，并允许完整的功能和结构解剖的H-mshi，我们还建议分离T辅助细胞克隆和血清抗体特异性反应的H-mshi+抗原。