GENETIC ASPECTS OF VIRAL ONCOGENESIS IN WILD MOUSE SPECIES

已知许多影响易感性的小鼠染色体基因。 小鼠对逆转录病毒诱导的肿瘤疾病的抵抗力。这些基因包括 内源性逆转录病毒序列，小鼠细胞基因有助于 或限制病毒复制，以及被病毒破坏的原癌基因 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， 我们获得了两性小鼠白血病病毒受体的分子克隆。 细胞表面受体，我们定义了该基因在 那只老鼠。我们还将HIV-1的阳性调节因子TRBP定位在 人和老鼠。在其他实验中，我们继续分析 涉及DBA/2J小鼠的几个杂交组合携带一个基因座Rmcf， 对水貂细胞病灶诱导(MCF)亚型的抗性负责 小鼠白血病病毒。确定了Rmcf的遗传图谱位置； 我们在卡斯特分枝杆菌亲本中发现了一个额外的抗性基因。 在这些映射到Chr1的相同的杂交中；我们识别了另外两个 在卡氏支原体中导致这种抗性的因素；我们是 利用Rmcf在连续回交中对卡氏沼虾的遗传 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，并应表征基因 卡氏支原体抗药性相关因素的研究。

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.