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: 3169901
• 负责人: SYAMAL K DATTA
• 金额: $ 28.62万
• 依托单位: TUFTS MEDICAL CENTER
• 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/3169901
• 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; lymphoma; murine leukemia virus; neoplasm /cancer genetics; oncogenes; scintillation counter; tissue /cell culture; virus genetics; virus morphology

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)

该研究项目的主要目标是确定基本原理 自身免疫性疾病和恶性淋巴瘤的发生机制 自身免疫 NZB 小鼠及其与正常 SWR 的杂交中自发产生的 老鼠。 NZB x SWR 交叉不仅被证明对于剖析有用 NZB菌株的各种异常在病因学中的作用 自身免疫性疾病，但也帮助我们识别因素 由狼疮性肾炎发展中的正常菌株所致。 几乎 100% 的 (NZB x SWR) F1 小鼠迅速发展为致命的严重疾病 肾小球肾炎，与其自身免疫性 NZB 父母形成鲜明对比。 通过杂交瘤从 F1 小鼠中获得单克隆抗 DNA 自身抗体 将分析技术的抗原结合特异性模式， 光谱型和同种异型。 编码的 F1 衍生自身抗体 由从 NZB 亲本继承的基因以及由 来自 SWR 亲本的抗体基因将被鉴定。 抗独特型 将产生针对这些自身抗体的特异性抗体。 这些 试剂将用于研究表达的遗传和调控 这些自身抗体独特型及其与肾炎发展的关系 NZB x SWR 交叉。这些自身抗体独特型将被故意 抑制肾炎的发生。 主要基因 确定自身免疫性疾病的发展将被识别并 通过构建小鼠的重组近交系和同类系进行绘制。 最后，为了明确淋巴恶性肿瘤的机制，细胞 将确定 NZB 淋巴瘤的起源。基因组结构 淋巴瘤产生的病毒将通过 T1 寡核苷酸进行分析 指纹识别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的重排 也将被研究。 （MI）