GENETIC ASPECTS OF VIRAL ONCOGENESIS IN WILD MOUSE SPECIES

野生小鼠病毒致癌的遗传方面

• 批准号: 3746499
• 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/3746499
• 关键词: Abelson leukemia virus; Mus musculus; animal breeding; animal genetic material tag; animal population genetics; cytogenetics; gene interaction; genetic mapping; host organism interaction; laboratory mouse; mouse mammary tumor virus; murine leukemia virus; neoplasm /cancer genetics; oncogenes; oncogenic virus; protooncogene; provirus; viral carcinogenesis; viral leukemogenesis; virus genetics; virus infection mechanism; virus receptors; virus related neoplasm /cancer

A number of mouse chromosomal genes have been described which affect the susceptibility of mice to retrovirus-induced neoplastic disease. These genes include endogenous retroviral sequences, mouse cellular genes which facilitate or restrict virus replication, and proto- oncogenes disrupted by viral insertion. In the process of characterizing new common viral insertions in tumors induced by Abelson and Moloney MuLVs, we identified two new integration sites on the same chromosome, Chromosome 10. We defined the close genetic and physical distance between these insertion sites and the previously described oncogene Myb on this Chromosome, but suggest that these insertions may disrupt other oncogenic sequences in this region. In other experiments, we began analysis of several crosses involving DBA/2J mice which carries a locus responsible for resistance to MCF subtype of viruses, Rmcf. We defined the genetic map location of Rmcf, we identified an additional resistance gene in these same crosses which maps to Chr 1, and we are following inheritance of Rmcf through serial backcrosses to M. castaneus which lacks endogenous MCF viruses. These experiments should help determine whether Rmcf represents an endogenous provirus expression of which blocks viral cell surface receptors. Finally, we used a fragment of the recently clone amphotropic viral cell surface receptor to map the mouse gene to Chromosome 8.

已经描述了许多小鼠染色体基因，其影响 小鼠对逆转录病毒诱导的肿瘤疾病的易感性。 这些基因包括内源性逆转录病毒序列、小鼠细胞基因、 促进或限制病毒复制的基因，以及 被病毒插入破坏的癌基因。 过程中 表征由以下物质诱导的肿瘤中的新的常见病毒插入 Abelson和Moloney MuLVs，我们确定了两个新的整合位点， 同一条染色体，十号染色体 我们定义了相近的基因， 这些插入部位和先前插入部位之间的物理距离 描述了该染色体上的癌基因Myb，但表明这些 插入可以破坏该区域中的其它致癌序列。 在 在其他实验中，我们开始分析几个杂交， DBA/2 J小鼠携带负责MCF抗性的基因座 病毒亚型Rmcf。 我们定义了 Rmcf，我们发现了一个额外的抗性基因，在这些相同的 交叉映射到Chr 1，我们正在跟踪Rmcf的遗传 通过一系列回交转基因到M缺乏内源性MCF的板栗 病毒 这些实验应该有助于确定Rmcf是否 代表内源性原病毒表达，其阻断病毒 细胞表面受体 最后，我们使用了最近的一个片段， 克隆嗜酸性病毒细胞表面受体，以定位小鼠基因， 八号染色体。