GENETIC ASPECTS OF VIRAL ONCOGENESIS IN WILD MOUSE SPECIES

小鼠的易感性各不相同 逆转录病毒和逆转录病毒引起的疾病。这些差异 是由于各种小鼠染色体基因，我们已经 参与了一项正在进行的研究， 在这种耐药性中，并确定耐药性的病毒靶点。在 一系列的实验中，我们一直在研究一种变体， 小鼠乳腺肿瘤病毒（MMTV）诱导T细胞 淋巴瘤这些肿瘤含有新的MMTV整合， 正在鉴定这些位点的细胞基因。的 到目前为止检查了4个集成，其中3个映射到不 与白血病病毒引起的淋巴瘤有关，但 第四个定位在c-myc附近，c-myc是一种明显参与肿瘤的原癌基因 白血病病毒诱导（达德利，亚当森）。我们继续 研究病毒抗性基因Rmcf，它负责 对白血病病毒的多变性类别的抗性。我们有 将这种抗性转移到野生小鼠的遗传背景中， 系列回交，并使用这些部分同源，以确定一个 紧密连接的染色体整合的病毒包膜拷贝。 这种病毒包膜是一种可能发挥作用的耐药候选物 通过阻断细胞表面的病毒受体。我们正致力于 克隆这个基因（Lyu，Lee）。我们已经开始研究一种血清 在大多数小鼠中发现的灭活白血病病毒的因子。我们 已经表明，这一因素并不影响病毒的传播。 嗜亲性和嗜亲性寄主范围组，但它强烈 灭活嗜多性病毒和较弱的异嗜性病毒。 我们已经确定，这个因素的存在是在单一的 基因控制，我们已经启动了基因组扫描，以确定 李（Lee）。野生鼠种M.栗色 与近交系的不同之处在于，这些小鼠对 多变性病毒这种阻力很可能是由于 细胞表面受体的变异。遗传杂交 现在表明，野生小鼠遗传中的其他基因 背景可能有助于这种阻力，我们是在 分析额外的遗传杂交以鉴定 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).