GENETIC ASPECTS OF VIRAL ONCOGENESIS IN WILD MOUSE SPECIES AND LABORATORY MICE

小鼠的基因组包含各种与病毒诱导有关的基因。 肿瘤疾病。这些基因包括内源性逆转录病毒序列，如 以及促进或限制病毒的小鼠细胞基因 复制。各种细胞基因也可以作为病毒受体发挥作用； 我们使用长臂猿白血病病毒(Galv)受体的人类基因来 鉴定同源序列并将其定位到小鼠2号染色体，这表明 与野生动物2号染色体编码受体Rec-2的可能同源性 小鼠逆转录病毒；我们还鉴定了GALV相关的多个拷贝 小鼠基因组中的序列表明该基因可能起了作用 作为MUS进化过程中的受体。 在其他实验中，我们确定了几种新的常见病毒整合 与肿瘤诱发相关的区域。的两个集成区 BL/LV3辐射白血病病毒被映射到小鼠的相反两端 6号染色体.定位的Friend MuLV的常见整合位点之一 在原癌基因位点Kras-2附近，以及位于或 接近FV-2抗性基因。为了确定可能的身份 在这些基因中，我们将这两个基因定位在同一个基因交叉中。这些实验 制作了FV-2基因座周围的分子遗传图谱，但未能 提供证据证明这两个可能是不同的基因座。 最后，我们使用了定点突变技术来改变 AKV MuLV的CAGag区，被认为与该基因相互作用 FV-1抗性基因的产物。结果表明，只有一种氨基 酸替代足以改变病毒的嗜性。其他变化包括 引入此站点，其中一些并未改变病毒复制 模式，其中一些模式将原始的N嗜性病毒转化为 特征的B嗜性病毒，其中一种产生了一种带有 不同近交系来源的细胞上的新复制模式和 野鼠物种。

The mouse genome contains various genes which are involved in virus-induced neoplastic disease. These genes include endogenous retroviral sequences as well as mouse cellular genes which facilitate or restrict virus replication. Various cellular genes can also function as viral receptors; we used the human gene for the gibbon ape leukemia virus (GALV) receptor to identify and map homologous sequences to mouse chromosome 2, suggesting a possible identity with Rec-2, the chromosome 2 encoded receptor for a wild mouse retrovirus; we also identified multiple copies of GALV-related sequences in the mouse genome suggesting that this gene may have functioned as a receptor during the evolution of Mus. In other experiments we identified several novel common viral integration regions associated with tumor induction. Two integration regions for BL/LV3 radiation leukemia virus were mapped to opposite ends of mouse chromosome 6. One of the common integration sites for Friend MuLV mapped near the protooncogene locus Kras-2, and a second Friend site maps at or near the Fv-2 resistance gene. In order to determine the possible identity of these genes we mapped both in the same genetic cross. These experiments produced a molecular genetic map around the Fv-2 locus and failed to provide evidence that the two may be distinct loci. Finally, we have used site specific mutagenesis to alter the site in the CAgag region of the AKV MuLV which is thought to interact with the gene product of the Fv-1 resistance gene. Results show that only a single amino acid substitution is sufficient to alter virus tropism. Other changes were introduced into this site, some of which did not alter virus replication patterns, some of which converted the original N-tropic virus into a characteristic B-tropic virus, and one of which produced a virus with a novel replication pattern on cells derived from various inbred strains and wild mouse species.