Resistance to friend virus-induced erythroleukemia in W/W(v) mice is caused by a spleen-specific defect which results in a severe reduction in target cells and a lack of Sf-Stk expression.
Resistance to friend virus-induced erythroleukemia in W/W(v) mice is caused by a spleen-specific defect which results in a severe reduction in target cells and a lack of Sf-Stk expression.
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W/W(v) 小鼠对友人病毒诱导的红白血病的抵抗力是由脾脏特异性缺陷引起的，该缺陷导致靶细胞严重减少和 Sf-Stk 表达缺乏。
DOI：
10.1128/jvi.79.23.14586-14594.2005
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发表时间：
2005
影响因子：
5.4
通讯作者：
Paulson,RobertF
中科院分区：
文献类型：
--
作者：
Subramanian,Aparna;Teal,HamiE;Correll,PamelaH;Paulson,RobertF
Friend病毒对红系的特征性进展和特异性允许鉴定疾病进展所需的许多宿主编码的基因座。这些基因座中的几个，包括Friend病毒易感基因2（Fv 2）、显性白色斑点基因（W）和Steel基因（S1），调节感染的红系祖细胞的初始多克隆扩增。WandSlen分别编码Kit受体酪氨酸激酶及其配体、干细胞因子。W突变小鼠严重贫血，早期的研究表明，这种红细胞分化缺陷是对Friend病毒诱导的红白血病产生抗性的原因。在这里，我们表明，在骨髓中，W/Wv小鼠具有接近正常数量的靶细胞，并且骨髓的初始感染在体内正常发生。与此相反，脾细胞从W/Wv小鼠在体外和体内感染Friend病毒未能产生红细胞生成素独立的集落在任何时间后Friend病毒感染，这表明突变的试剂盒受体特异性地影响靶细胞在脾脏中，使突变小鼠耐Friend病毒诱导的红白血病的发展。此外，我们发现Friend病毒在脾脏中的Kit+致病靶点与骨髓中的致病靶点不同，并且这种脾脏靶细胞群体在W/Wv小鼠中显著减少，并且这些细胞不能表达Sf-Stk。这些结果还强调了脾脏微环境在支持Friend病毒感染小鼠急性白血病进展中的作用的独特性质。
The characteristic progression and specificity of Friend virus for the erythroid lineage have allowed for the identification of a number of host-encoded loci that are required for disease progression. Several of these loci, including the Friend virus susceptibility gene 2 (Fv2), dominant white spotting gene (W), and Steel gene (Sl), regulate the initial polyclonal expansion of infected erythroid progenitor cells.WandSlencode the Kit receptor tyrosine kinase and its ligand, stem cell factor, respectively.Wmutant mice are severely anemic, and earlier work suggested that this defect in erythroid differentiation is the cause for the resistance to Friend virus-induced erythroleukemia. Here we show that in bone marrow,W/Wvmice have near normal numbers of target cells and the initial infection of bone marrow occurs normally in vivo. In contrast, spleen cells fromW/Wvmice infected both in vitro and in vivo with Friend virus failed to give rise to erythropoietin-independent colonies at any time following Friend virus infection, suggesting that mutation of the Kit receptor specifically affects target cells in the spleen, rendering the mutant mice resistant to the development of Friend virus-induced erythroleukemia. In addition, we show that the Kit+pathogenic targets of Friend virus in the spleen are distinct from the pathogenic targets in bone marrow and this population of spleen target cells is markedly decreased inW/Wvmice and these cells fail to expressSf-Stk. These results also underscore the unique nature of the spleen microenvironment in its role in supporting the progression of acute leukemia in Friend virus-infected mice.