CONTROL OF RESISTANCE TO VIRAL LEUKOMOGENESIS IN WILD MOUSE POPULATIONS

控制野生小鼠群体对病毒性白血病发生的抗性

• 批准号: 3818177
• 负责人: C A KOZAK
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3818177
• 关键词: Mus musculus; Retroviridae disease; animal population genetics; disease /disorder proneness /risk; genetic regulation; genetic strain; immunoregulation; laboratory mouse; molecular cloning; molecular oncology; molecular pathology; murine leukemia virus; neoplasm /cancer genetics; nucleic acid sequence; oncogenes; oncogenic virus; provirus; viral leukemogenesis; virus genetics; virus infection mechanism; virus protein; virus related neoplasm /cancer

Analysis of the genetic basis of virus induced neoplastic disease has led to the identification of many chromosomal genes involved in these processes. Although most of these studies rely on use of the various inbred strains, we have begun to analyze a number of wild mice for infectious MuLVs and for susceptibility to virus induced disease. We have identified a novel infectious MuLV, termed HoMuLV, found in the European wild mouse M. hortulanus. HoMuLV has an ecotropic host range and induces neoplastic disease in NIH Swiss mice. HoMuLV was molecularly cloned and sequenced, and its gp70 and several gag proteins were shown to differ substantially from those of the known ecotropic MuLVs. In another series of experiments, we examined various wild derived mice which contained few copies of a single type of germline provirus for susceptibility to virus induced disease. In particular, M. spretus does not produce infectious virus nor does it express detectable levels of retrovirus-related RNA. However, this mouse produces infectious MCF recombinant virus 5 weeks after inoculation with MCF MuLV and develops lymphoma within 16 weeks. Thus, this mouse contains the endogenous sequences which can contribute to the generation of leukemogenic MuLVs. One germline spretus provirus has been molecularly cloned and is being characterized.

病毒性肿瘤的遗传学基础分析 已经鉴定出许多与此相关的染色体基因 在这些过程中。 虽然这些研究大多依赖于使用 各种近交系，我们已经开始分析一些 野生小鼠的感染性MuLV和对病毒的易感性 诱发疾病。 我们发现了一种新型的感染性MuLV， 命名为HoMuLV，发现于欧洲野生小鼠M. hortulanus HoMuLV具有嗜亲性宿主范围并诱导肿瘤性疾病 在瑞士国家卫生研究院的老鼠身上。 对HoMuLV进行了分子克隆和测序， 并且其gp70和几种gag蛋白被证明存在差异 基本上与已知的亲嗜性MuLV的那些不同。 在另一 在一系列实验中，我们检查了各种野生小鼠， 包含几个单一类型的生殖系原病毒拷贝， 对病毒引起的疾病易感。 特别是M.斯普雷图斯 不产生感染性病毒，也不表达可检测的 逆转录病毒相关RNA的水平。 然而，这只老鼠产生 接种MCF后5周感染性MCF重组病毒 MuLV并在16周内发展为淋巴瘤。 因此，这只老鼠 含有内源性序列，这些序列可以有助于 产生白血病性MuLV。 一个生殖系前病毒 已经被分子克隆并被鉴定。