Suzuki S, Axelrad A A
Cell. 1980 Jan;19(1):225-36. doi: 10.1016/0092-8674(80)90404-3.
We have found that Fv-2 on chromosome 9 of the mouse, the locus originally identified as a major determinant of host susceptibility (Fv-2s) or resistance (Fv-2r) to Friend leukemia virus in mice, also functions in uninfected animals, where it determines whether a high (Fv-2s) or low (Fv-2r) proportion of erythropoietic progenitor cells BFU-E are normally engaged in DNA synthesis. Adult mice belonging to five inbred strains of genotype Fv-2rr, two inbred strains and three congenic strains of genotype Fv-2ss, two kinds of F1 hybrid of genotype Fv-2rs, and appropriate controls were given high specific activity 3H--thymidine intravenously for 1 hr and their bone marrow and spleen cells were assayed for surviving BFU-E at 7 days and CFU-E at 2 days in plasma culture. A high proportion of BFU-E in all Fv-2ss and Fv-2rs mice were killed, but all or nearly all of the BFU-E in Fv-2rr mice survived exposure to 3H--thymidine. The allelic difference of Fv-2 had no significant effect on the proportion of other progenitor or stem cells (CFU-E, CFU-C or CFU-S) normally undergoing DNA synthesis in the hemopoietic tissues, or on the hemoglobin concentration, red blood cells, hematocrit, total of differential white blood cell counts in the peripheral blood of these animals. While a few or no BFU-E were killed by 3H--thymidine in adult B6 (Fv-2rr) mice, a high proportion of BFU-E were killed by 3H--thymidine in these animals when they were less than 7 weeks old. Bleeding of adult B6 mice or lethal irradiation followed by repopulation by syngeneic bone marrow cells rendered a high proportion of their BFU-E vulnerable to 3H--thymidine. BFU-E of adult B6 mice which in vivo were unaffected by 3H--thymidine were rapidly killed when exposed to 3H--thymidine in vitro. Fv-2 thus seems to act at or near the G1-S or G0-S boundary to influence the rate or probability of transition between the nonDNA-synthesizing and the DNA-synthesizing states of BFU-E. The gene that controls susceptibility or resistance to a murine erythroleukemia virus appears also to be a regulatory gene that controls the proliferative behaviour of normal cells at a specific stage of erythropoietic differentiation.
我们发现，小鼠9号染色体上的Fv-2，该位点最初被确定为小鼠对Friend白血病病毒宿主易感性（Fv-2s）或抗性（Fv-2r）的主要决定因素，在未感染的动物中也发挥作用，它决定了高比例（Fv-2s）或低比例（Fv-2r）的红细胞生成祖细胞BFU-E正常参与DNA合成。将属于五种Fv-2rr基因型近交系、两种Fv-2ss基因型近交系和三种同源系、两种Fv-2rs基因型F1杂种的成年小鼠以及适当的对照静脉注射高比活度的3H-胸腺嘧啶1小时，7天后测定其骨髓和脾细胞中存活的BFU-E，2天后在血浆培养中测定CFU-E。所有Fv-2ss和Fv-2rs小鼠中高比例的BFU-E被杀死，但Fv-2rr小鼠中所有或几乎所有的BFU-E在暴露于3H-胸腺嘧啶后存活下来。Fv-2的等位基因差异对造血组织中正常进行DNA合成的其他祖细胞或干细胞（CFU-E、CFU-C或CFU-S）的比例，或对这些动物外周血中的血红蛋白浓度、红细胞、血细胞比容、白细胞分类计数总和均无显著影响。虽然成年B6（Fv-2rr）小鼠中少数或没有BFU-E被3H-胸腺嘧啶杀死，但当这些动物小于7周龄时，高比例的BFU-E被3H-胸腺嘧啶杀死。成年B6小鼠放血或致死性照射后用同基因骨髓细胞重新填充，使其高比例的BFU-E易受3H-胸腺嘧啶的影响。成年B6小鼠体内不受3H-胸腺嘧啶影响的BFU-E在体外暴露于3H-胸腺嘧啶时会迅速被杀死。因此，Fv-2似乎在G1-S或G0-S边界处或附近起作用，以影响BFU-E在非DNA合成状态和DNA合成状态之间转变的速率或概率。控制对鼠红细胞白血病病毒易感性或抗性的基因似乎也是一个调控基因，它在红细胞生成分化的特定阶段控制正常细胞的增殖行为。
