Genetic and viral factors influencing the development of spontaneous leukemia in AKR mice.
Genetic and viral factors influencing the development of spontaneous leukemia in AKR mice.
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DOI：
10.1016/0042-6822(79)90184-3
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发表时间：
1979-07
期刊：
影响因子：
3.7
通讯作者：
R. Nowinski;M. Brown;T. Doyle;R. Prentice
中科院分区：
文献类型：
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作者：
R. Nowinski;M. Brown;T. Doyle;R. Prentice
影响自发性白血病发展的因素进行了研究，在一个遗传交叉，白血病倾向的AKR和白血病耐药的C57 BL/6小鼠之间的准备。对200只AKR x（C57 BL/6 x AKR）F1回交小鼠进行了以下检查：（a）内源性嗜N性鼠白血病病毒（MuLV）的产生，（B）抗病毒抗体的产生，（c）主要组织相容性复合体（MHC）的表型，（d）Fv-1（Gpd-1）区域的表型，以及（e）白血病或其他自然原因导致的死亡率。尽管该杂交小鼠含有至少一种AKR亲嗜性穆尔V的遗传互补，并且预期产生高水平的感染性病毒，但多种次要因素影响了在细胞外液中可检测到的MuLV水平。亲嗜性MuLV在个别小鼠的滴度被发现强烈，同时与Fv-1（GPD-1）表型和血清中的抗病毒抗体的滴度。因此，感染性MuLV的水平在Fv-1 n/b基因型小鼠和产生高滴度抗gp 70抗体的小鼠中显著较低。另一方面，抗gp 70抗体的产生受小鼠MHC表型和性别的独立调节。发现高抗体滴度与MHCb/k单倍型和女性相关。在24个月期间获得的存活数据用于确定病毒表达与胸腺白血病、非胸腺白血病和其他自然原因引起的死亡之间的关联。回归分析表明，定位在Fv-1（Gpd-1）区域内的基因是胸腺白血病死亡风险的最重要的决定因素。尽管与嗜亲性MuLV的高产量相关的死亡率存在轻微的累加效应，但似乎由Fv-1（Gpd-1）区域中的基因控制的其他因素是AKR小鼠对胸腺白血病的显著易感性的主要原因。虽然这些因素的存在表明，在这项研究中，他们的作用模式没有定义。此外，还发现抗病毒抗体的产生影响胸腺白血病引起的死亡率。然而，这种关联在很大程度上可以用可检测的亲嗜性MuLV水平与抗gp 70抗体滴度之间存在的反比关系来解释。最后，我们注意到非胸腺性白血病引起的死亡率并不受Fv-1（Gpd-1）区域或亲嗜性MuLV表达的表型变异的显著影响。这一发现表明，胸腺和非胸腺起源的白血病有不同的病因。
Factors influencing the development of spontaneous leukemia were studied in a genetic cross that was prepared between leukemia-prone AKR and leukemia-resistant C57BL/6 mice. Two hundred mice of the AKR x (C57BL/6 x AKR)F1backcross were examined for (a) the production of endogenous N-ecotropic murine leukemia virus (MuLV), (b) the production of anti-viral antibodies, (c) phenotype at the major histocompatibility complex (MHC), (d) phenotype at the Fv-1(Gpd-1) region, and (e) mortality due to leukemia or other natural causes. Although mice of this cross contained at least one genetic complement of AKR ecotropic MuL V and were expected to produce high levels of infectious virus, a variety of secondary factors influenced the level of MuLV that was detectable in extracellular fluids. The titer of ecotropic MuLV in individual mice was found to relate strongly and simultaneously to the Fv-1(Gpd-1) phenotype and to the titer of anti-viral antibodies in sera. Thus, the levels of infectious MuLV were significantly lower in mice of the Fv-1n/bgenotype and in mice that produced high titers of anti-gp70 antibodies. The production of anti-gp70 antibodies, on the other hand, was regulated independently by the MHC phenotype and the sex of the mouse. High antibody titers were found to be associated with the MHCb/khaplotype and with the female sex. Survival data derived during a 24 month period were used to determine associations between virus expression and death caused by thymic leukemia, nonthymic leukemia, and other natural causes. Regression analysis indicated that genes which mapped within the Fv-1(Gpd-1) region were the most important determinants of the risk of thymic leukemia mortality. Although there was a mild additive effect on mortality associated with the high production of ecotropic MuLV, it appeared that additional factors controlled by genes in the Fv-1(Gpd-1) region were most responsible for the dramatic susceptibility of AKR mice to thymic leukemias. Although the presence of these factors were indicated in this study, their mode of action was not defined. In addition, it was also found that the production of anti-viral antibodies influenced the mortality caused by thymic leukemias. This association, however, could be largely explained by the inverse relationship that existed between the level of detectable ecotropic MuLV and the titer of anti-gp70 antibodies. Last, it was noted that mortality caused by nonthymic leukemias was not significantly influenced by phenotypic variation in either the Fv-1(Gpd-1) region or in the expression of ecotropic MuLV. This finding suggested that leukemias of thymic and nonthymic origin had different etiologies.