Stewart M, Terry A, O'Hara M, Cameron E, Onions D, Neil J C
Molecular Oncology Laboratory, Department of Veterinary Pathology, University of Glasgow, Veterinary School, Bearsden, UK.
J Gen Virol. 1996 Mar;77 ( Pt 3):443-6. doi: 10.1099/0022-1317-77-3-443.
Moloney murine leukaemia virus (MoMLV) markedly accelerates thymic lymphoma development in mice carrying a transgene in which the human c-myc gene is linked to the CD2 locus control region. To investigate the mechanism of synergy and identify the genes which collaborate with myc in these clonal tumours, we analysed the sites of MoMLV insertion. Analysis of known viral integration loci revealed only a small number of insertions at bmi-1, pim-1 and ahi-1. Further cloning and hybridization analysis revealed a new common integration locus, designated til-1, which was occupied in 25 out of 77 lymphomas examined, with evidence of multiple clonal insertions in some cases. Mapping relative to established chromosomal markers in interspecific backcross mice located til-1 to mouse chromosome 17, distal to pim-1 and tic-1. These results suggest that the til-1 locus may harbour a novel myc-collaborating gene which acts as a target for activation in T cell lymphomas.
莫洛尼鼠白血病病毒(MoMLV)能显著加速携带一种转基因的小鼠胸腺淋巴瘤的发展,该转基因中人类c-myc基因与CD2基因座控制区相连。为了研究协同作用的机制并鉴定在这些克隆性肿瘤中与myc协同作用的基因,我们分析了MoMLV的插入位点。对已知病毒整合位点的分析显示,只有少数插入发生在bmi-1、pim-1和ahi-1基因处。进一步的克隆和杂交分析揭示了一个新的共同整合位点,命名为til-1,在所检测的77个淋巴瘤中有25个含有该位点,在某些情况下有多个克隆插入的证据。相对于种间回交小鼠中已确定的染色体标记进行定位,将til-1定位于小鼠17号染色体,位于pim-1和tic-1的远端。这些结果表明,til-1位点可能含有一个新的与myc协同作用的基因,该基因在T细胞淋巴瘤中作为激活靶点发挥作用。