GENETIC-VIRAL-IMMUNOLOGIC STUDIES IN NEW ZEALAND MICE

新西兰小鼠的遗传病毒免疫学研究

• 批准号: 3169908
• 负责人: SYAMAL K DATTA
• 金额: $ 29.36万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3169908
• 关键词: B lymphocyte; Retroviridae disease; T lymphocyte; antiantibody; antibody formation; antibody specificity; antigen antibody reaction; antiidiotype antibody; autoantibody; autoimmune disorder; biological models; cellular oncology; electrofocusing; endonuclease; gene expression; genetic mapping; genetic regulation; glomerulonephritis; hybridomas; immunogenetics; immunoprecipitation; immunoregulation; laboratory mouse; lymphoma; murine leukemia virus; neoplasm /cancer genetics; oncogenes; scintillation counter; tissue /cell culture; virus genetics; virus morphology; virus protein

The major goal of this research project is to determine the fundamental mechanisms of autoimmune disease and malignant lymphomas that develop spontaneously in autoimmune NZB mice and their crosses with the normal SWR mice. The NZB x SWR crosses have not only proved useful to dissect the role of various abnormalities of the NZB strain in the etiology of autoimmune disease, but are also helping us to identify the factors contributed by a normal strain in the development of lupus nephritis. AImost 100% of (NZB x SWR) F1 mice rapidly develop a lethally severe glomerulonephritis, in marked contrast to their autoimmune NZB parents. Monoclonal anti-DNA autoantibodies derived from the F1 mice by hybridoma technology will be analyzed for their antigen-binding specificity patterns, spectrotypes and allotypes. The F1-derived autoantibodies that are encoded by genes inherited from the NZB parent and those that are encoded by antibody genes from the SWR parent will be identified. Anti-idiotypic antibodies specific for these autoantibodies will be raised. These reagents will be used to study the inheritance and regulation of expression of these autoantibody idiotypes and their relation to nephritis development in NZB x SWR crosses. These autoantibody idiotypes will be deliberately suppressed to prevent the development of nephritis. The major genes determining the development of autoimmune disease will be identified and mapped by constucting recombinant inbred and congenic lines of mice. Finally, to define the mechanism of lymphoid malignancy, the cellular origin of the NZB lymphomas will be determined. The genomic structure of viruses produced by the lymphomas will be analyzed by T1 oligonucleotide fingerprinting and restriction endonuclease mapping techniques. Rearrangement of retroviral genes and cellular oncogenes in the lymphomas will also be studied. (MI)

本研究项目的主要目标是确定 自身免疫性疾病和恶性淋巴瘤的发病机制 在自身免疫NZB小鼠及其与正常SWR的杂交中自发地 小鼠 NZB x SWR杂交不仅被证明有助于解剖 NZB菌株的各种异常在 自身免疫性疾病，但也帮助我们确定的因素， 狼疮性肾炎是由正常的狼疮性肾炎引起的。 几乎100%的（NZB x SWR）F1小鼠迅速发展为致死性重度 肾小球肾炎，与自身免疫性NZB父母形成鲜明对比。 用杂交瘤技术制备抗DNA单克隆抗体 技术将分析其抗原结合特异性模式， spectrotypes和allotypes。 编码的F1衍生自身抗体 由遗传自NZB亲本的基因和那些由 将鉴定来自SWR亲本的抗体基因。 抗独特 将产生对这些自身抗体特异的抗体。 这些 试剂将用于研究遗传和表达调控 这些自身抗体独特型及其与肾炎发展的关系 在NZB x SWR的十字架。这些自身抗体独特型将被故意 抑制以防止肾炎的发展。 主基因 确定自身免疫性疾病的发展将被确定， 通过构建小鼠的重组近交系和同源系来作图。 最后，为了明确淋巴恶性肿瘤的机制，细胞免疫学检查显示， 将确定NZB淋巴瘤的起源。的基因组结构 将通过T1寡核苷酸分析淋巴瘤产生的病毒 指纹图谱和限制性内切酶图谱技术。 淋巴瘤中逆转录病毒基因和细胞癌基因重排的研究 也将被研究。 （密歇根州）