GENETIC ASPECTS OF VIRAL ONCOGENESIS IN WILD MOUSE SPECIES

小鼠之间的敏感度不同 到逆转录病毒和逆转录病毒引起的疾病。这些差异 是由于不同的小鼠染色体基因所致，我们已经 参与了一项持续的努力，以确定相关的小鼠基因 在这种抗性中，并找出病毒的抗性靶点。在……里面 在一系列实验中，我们一直在研究一种变体 诱导T细胞的小鼠乳腺肿瘤病毒(MMTV) 淋巴瘤。这些肿瘤包含新的MMTV整合和我们 正在鉴定这些部位的细胞基因。中的 到目前为止检查了4个集成，其中3个映射到未 与白血病病毒的淋巴增生性有关，但 第四张地图靠近c-myc，这是一个明显与肿瘤有关的原癌基因 白血病病毒(Dudley，Adamson)诱导。我们继续 研究病毒抗性基因Rmcf，它负责 对多变型白血病病毒的抵抗力。我们有 通过将这种抗性转移到野鼠的遗传背景中 并使用这些部分基因来识别一个 紧密相连的病毒包膜的染色体整合拷贝。 这种病毒包膜是一种可能起作用的抗药性候选者 通过阻断细胞表面的病毒受体。我们正在研究 克隆这个基因(Lyu，Lee)。我们已经开始了对一种血清的研究 在大多数小鼠中发现的一种能灭活白血病病毒的因子。我们 已经表明，这一因素并不能灭活 生性和两性寄主范围群，但它强烈地 灭活多嗜性病毒和异嗜性病毒(强度较低)。 我们已经确定这一因素的存在是单一的 基因控制，我们已经启动了基因组扫描，以确定 负责地点(李)。野生鼠种卡氏支原体 与近交系小鼠的不同之处在于这些小鼠对 多变病毒。这种阻力很可能是由于 细胞表面受体的改变版本。遗传杂交 现在表明野鼠基因中的额外基因 背景可能是造成这种阻力的原因，而我们正处于 分析额外的遗传杂交以识别 这些基因的数量和染色体分布(Lee)。

Mice differ from one another in their susceptibility to retroviruses and retrovirus-induced diseases. These differences are due to various mouse chromosomal genes, and we have been engaged in an ongoing effort to characterize mouse genes involved in this resistance, and to identify the viral targets of resistance. In one series of experiments, we have been working on a variant mouse mammary tumor virus (MMTV) which induces T- cell lymphoma. These tumors contain novel MMTV integrations and we are in the process of identifying cellular genes at these sites. Of the 4 integrations examined to date, 3 of these map to regions not implicated in lymphomagenesis by the leukemia viruses, but the fourth maps near c-myc, a protooncogene clearly involved in tumor induction by leukemia viruses (Dudley, Adamson). We continued to investigate the viral resistance gene, Rmcf, which is responsible for resistance to the polytropic class of leukemia viruses. We have transferred this resistance to a wild mouse genetic background by serial backcrossing and used these partial congenics to identify a tightly linked chromosomally integrated copy of the viral envelope. This viral envelope is a candidate for resistance that may function by blocking cell surface viral receptors. We are working on the cloning this gene (Lyu, Lee). We have initiated studies on a serum factor found in most mice which inactivates leukemia viruses. We have shown that this factor does not inactivate viruses of the ecotropic and amphotropic host range groups, but that it strongly inactivates polytropic viruses and, less strongly, xenotropic viruses. We have determined that the presence of this factor is under single gene control and we have initiated a genome scan to identify the responsible locus (Lee). The wild mouse species M. castaneus differs from inbred strains in that these mice are resistant to polytropic viruses. This resistance is most likely due to the presence of an altered version of the cell surface receptor. Genetic crosses now suggest that additional genes in the wild mouse genetic background may contribute to this resistance, and we are in the process of analyzing additional genetic crosses to identify the number and chromosomal distribution of these genes (Lee).