MAJOR HISTOCOMPATIBILTY COMPLEX--AGING & TRANSGENIC MICE

主要组织相容性复合体——衰老

• 批准号: 3120722
• 负责人: ROY L. WALFORD
• 金额: $ 20.94万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3120722
• 关键词: DNA repair; MHC class I antigen; MHC class II antigen; aging; benzopyrenes; catalase; cell growth regulation; cell mediated lymphocytolysis test; flow cytometry; gene expression; genetic manipulation; genetically modified animals; immunoprecipitation; inbreeding; laboratory mouse; major histocompatibility complex; molecular genetics; superoxide dismutase; tumor necrosis factor alpha; unspecific monooxygenase

We have generated much evidence of both a "direct" and an "indirect" nature that the major histocompatibility complex (MHC) influences the aging rate, and some evidence that these effects map to the D and possibly K-A regions of H-2 in mice. Aim now is to carry forward studies of the relation of the MHC to aging by making transgenic Mus with genes cloned from the MHC of the long-lived (7-8 year) rodent Peromyscus leucopus. Genes from the D-end-like segment of Peromyscus MHC will utilized, including class I genes, TNF, and gene sequences from the same region whose possible functions are not yet specified but may relate to "non- immune" aspects of the MHC. The peromyscus-> Mus transgenics will be studied for Peromyscus MHC gene and gene product expression and function by neurological technics (immunoprecipitation, flow cytometry, restriction in cytotoxicity), for reproductive senescence, life span and diseases (especially tumor incidences), mRNA levels in several organs for SOD, catalase, mixed function oxidases, class I and II antigens, and tumor necrosis factor (all of which are known to be related to both aging and to the MHC), and repair of DNA adducts following injection of benzo (a)pyrene-trans-7,8-diol, which pilot studies suggests are also both age and MHC related. Further inbreeding of Peromyscus and serologic and molecular genetic studies of Peromyscus MHC will also be done, as adjunct to the above studies.

我们已经为“直接”和“间接”提供了很多证据 主要的组织相容性复合物（MHC）影响 老化率，以及一些证据表明这些效果映射到D，可能是 小鼠H-2的K-A区域。 现在的目的是对 通过用克隆的基因使转基因MUS与MHC与衰老的关系 从长寿（7 - 8年）的啮齿动物Peromyscus leucopus的MHC中。 Peromyscus MHC的D-End段的基因将使用， 包括I类基因，TNF和来自同一区域的基因序列 其可能的功能尚未指定，但可能与“非 - MHC的免疫”方面。 研究了Peromyscus MHC基因和基因产物表达和功能 通过神经技术技术（免疫沉淀，流式细胞术，限制 在细胞毒性中），用于生殖衰老，寿命和疾病 （尤其是肿瘤发病率），几个器官的mRNA水平用于SOD， 过氧化氢酶，混合功能氧化酶，I类和II抗原以及肿瘤 坏死因子（所有这些因子都与衰老和衰老有关 MHC），并在注射苯并后修复DNA加合物 （a）pyrene-trans-7,8-二醇，试点研究表明，这都是年龄的 和MHC相关。 peromyscus和Serologic and Chered inbreded and 在辅助 上述研究。