Ramirez Jean Marie, Houzet Laurent, Koller Richard, Bies Juraj, Wolff Linda, Mougel Marylène
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS UMR5121, UMI, IFR122, Montpellier, France.
Virology. 2004 Dec 20;330(2):398-407. doi: 10.1016/j.virol.2004.09.038.
Alternative splicing in Mo-MuLV recruits a splice donor site, SD', within the gag that is required for optimal replication in vitro. Remarkably, this SD' site was also found to be utilized for production of oncogenic gag-myb fusion RNA in 100% of murine-induced myeloid leukemia (MML) in pristane-treated BALB/c mice. Therefore, we investigated the influence of silent mutations of SD' in this model. Although there was no decrease in the overall incidence of disease, there was a decrease in the incidence of myeloid leukemia with a concomitant increase in lymphoid leukemia. Importantly, there was a complete lack of myeloid tumors associated with 5' insertional mutagenic activation of c-myb, suggesting the specific requirement of the SD' site in this mechanism.
莫洛尼鼠白血病病毒（Mo-MuLV）中的可变剪接在gag基因内招募了一个剪接供体位点SD'，该位点是体外最佳复制所必需的。值得注意的是，在经 pristane 处理的 BALB/c 小鼠中，100%的鼠源性髓系白血病（MML）中该SD'位点也被用于致癌性gag-myb融合RNA的产生。因此，我们在该模型中研究了SD'沉默突变的影响。虽然疾病的总体发病率没有降低，但髓系白血病的发病率下降，同时淋巴系白血病的发病率上升。重要的是，完全没有与c-myb的5'插入诱变激活相关的髓系肿瘤，这表明该机制中SD'位点的特殊需求。
