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: 5200432
• 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/5200432
• 关键词: Mus musculus; animal genetic material tag; animal population genetics; genetic mapping; host organism interaction; laboratory mouse; murine leukemia virus; neoplasm /cancer genetics; oncogenes; oncogenic virus; protooncogene; provirus; viral carcinogenesis; virus genetics; virus infection mechanism; virus receptors

Many mouse chromosomal genes are known 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. We have been using standard classical genetics to identify and map genes involved in these phenomena. In one series of experiments, we obtained a molecular clone of the receptor for the amphotropic MuLV cell surface receptor, and we defined the map location of this gene in the mouse. We have also mapped TRBP, a positive regulator of HIV-1, in man and mouse. In other experiments, we have continued analysis of several crosses involving DBA/2J mice which carry a locus, Rmcf, responsible for resistance to the mink cell focus inducing (MCF) subtype of mouse leukemia viruses. We defined the genetic map location of Rmcf; we identified an additional resistance gene in the M. castaneus parent of these same crosses which maps to Chr 1; we identified two additional factors which contribute to this resistance in M. castaneus; and we are following inheritance of Rmcf in 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, and should characterize the genetic factors responsible for resistance in M. castaneus.

已知许多影响易感性的小鼠染色体基因 小鼠逆转录病毒诱导的肿瘤疾病。这些基因包括 内源性逆转录病毒序列，小鼠细胞基因， 或限制病毒复制，原癌基因被病毒破坏， 插入。 我们一直在使用标准的经典遗传学来鉴定 并绘制与这些现象有关的基因图谱。 在一系列实验中， 我们获得了嗜中性MuLV受体的分子克隆， 细胞表面受体，我们确定了该基因的地图位置， 鼠标 我们还绘制了TRBP，一种HIV-1的正调节因子， 人和老鼠在其他实验中，我们继续分析了 几个涉及DBA/2 J小鼠的杂交，这些小鼠携带一个基因座，Rmcf， 负责抵抗水貂细胞病灶诱导（MCF）亚型 小鼠白血病病毒。 确定了Rmcf的遗传图谱定位; 我们在M.栗树亲本 这些相同的交叉映射到Chr 1;我们确定了两个额外的 这些因素导致了M.栗;我们是 在与M的连续回交中Rmcf遗传之后。栗色， 缺乏内源性MCF病毒。 这些实验应该有助于确定 Rmcf是否代表内源性前病毒，其表达 阻断病毒细胞表面受体，并应表征遗传 M.栗色的