GENETIC ASPECTS OF VIRAL ONCOGENESIS IN WILD MOUSE SPECIES

近交系小鼠和野生小鼠物种在它们的 对逆转录病毒和逆转录病毒引起的疾病的易感性。 这些 差异归因于不同的小鼠染色体基因 包括内源性逆转录病毒序列、 促进或限制病毒复制，原癌基因被破坏 通过病毒插入。 我们一直在使用标准的经典遗传学， 鉴定和绘制与这种抗性有关的基因。 在一系列的 实验中，我们确定了抗性的遗传图谱位置， Rmcf基因。 在同一项研究中，我们还发现了一种额外的 野生小鼠中致白血病MCF病毒的抗性基因 种M.栗色的 我们将该基因定位于Chr 1，并认为它 可以是编码细胞表面受体的基因的等位基因变体 for this subgroup亚组of viruses病毒. 在一系列扩大的基因杂交中 对于这只野生老鼠，我们发现了两个额外的因素， 有助于M中的这种阻力。卡斯塔纽斯，我们正在跟踪 Rmcf在与M.栗色，缺乏 内源性MCF病毒。 这些实验应该有助于确定 Rmcf代表一种内源性前病毒，其表达可阻断病毒 细胞表面受体，并应表征遗传因素 在M.栗色的在其他研究中，我们 有助于克隆和表征的小鼠同源物 白血病相关的PML基因 我们还确定了基因图谱 肿瘤特异性乳腺病毒整合位点Int6的位置和 在这个过程中，证明了这个整合位点不同于 与肿瘤发生有关的其他染色体基因。 最后我们 确定了最初称为Dis1和Dis2的特异性插入位点， 小鼠艾滋病病毒在其感染的目标B细胞。 遗传作图 表明Dis1可能与Sfpi 1相同，Sfpi 1是插入位点， 先前在Friend病毒诱导的红白血病中发现。 的 第二个位点，Dis2，定位于Chr 11，似乎含有一个新基因 参与B细胞增殖。

Inbred strains of mice and wild mouse species differ in their susceptibility to retroviruses and retrovirus-induced diseases. These differences have been attributed to various mouse chromosomal genes including 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 this resistance. In one series of experiments, we determined the genetic map location of the resistance gene Rmcf. In the same study, we also identified an additional resistance gene for the leukemogenic MCF viruses in the wild mouse species M. castaneus. We mapped this gene to Chr 1 and suggest that it may be an allelic variant of the gene encoding the cell surface receptor for this subgroup of viruses. In an expanded series of genetic crosses with this wild mouse, 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. In other studies, we contributed to the cloning and characterization of the murine homolog of the leukemia-associated PML gene. We also determined the genetic map location for the tumor specific mammary virus integration site Int6 and in the process demonstrated that this integration site is distinct from other chromosomal genes involved in tumorigenesis. Finally, we identified specific insertion sites initially termed Dis1 and Dis2 for the murine AIDS virus in its infected target B cell. Genetic mapping suggested that Dis1 may be identical to Sfpi1, an insertion site previously identified in erythroleukemias induced by Friend virus. The second site, Dis2, mapped to Chr 11, and appears to harbor a novel gene involved in B-cell proliferation.