Rapid induction of B-cell lymphomas in mice carrying a human IgH/c-mycYAC
Rapid induction of B-cell lymphomas in mice carrying a human IgH/c-mycYAC
复制标题
DOI：
10.1038/sj.onc.1200968
复制
发表时间：
1997-03-20
期刊：
影响因子：
8
通讯作者：
Bruggemann, M
中科院分区：
文献类型：
--
作者：
Butzler, C;Zou, XG;Bruggemann, M
染色体易位后，c-myc原癌基因被免疫球蛋白（IG）位点之一激活是伯基特淋巴瘤的一贯特征。这种肿瘤的不同亚型在易位区的分子结构上不同。在大多数情况下，没有已知的邻近癌基因的IG基因座的调节元件，这在很大程度上模糊了其失调的机制。为了评估可能的癌基因激活信号，我们通过在含有人IG重链（IgH）基因座的220 kb区域的酵母人工染色体（YAC）中从IgH内含子增强子插入约50 kb的c-myc基因来产生实验易位区域。通过原生质球融合将该YAC单拷贝整合到小鼠胚胎干（ES）细胞的基因组中。来自这些ES细胞的嵌合小鼠在8-16周龄时发展出表达表面IgM的单克隆B细胞淋巴瘤。IgH/c-myc转座在几乎所有的肿瘤中都表现出不同的V（H）DJ（H）重排，而c-myc和IgH内含子增强子之间的距离没有任何改变。该小鼠模型可用于c-myc失调和IgH基因座在异常重排中的肿瘤形成能力的体内分析。
Activation of the c-myc proto-oncogene by one of the imnunoglobulin (Ig) loci after chromosomal translocation is a consistent feature of Burkitt's lymphoma. Different subtypes of this tumor vary in the molecular architecture of the translocation region. In most cases there are no known regulatory elements of the Ig locus neighboring the oncogene and this considerably obscures the mechanism of its deregulation. In order to assess possible oncogene activation signals, we produced an experimental translocation region by insertion of a c-myc gene about 50 kb from the IgH intron enhancer in a yeast artificial chromosome (YAC) containing a 220 kb region of the human Ig heavy chain (IgH) locus. Single copy integration of this YAC into the genome of mouse embryonic stem (ES) cells was achieved by spheroplast fusion. Chimeric mice derived from these ES cells developed monoclonal B-cell lymphomas expressing surface IgM by 8-16 weeks of age. The IgH/c-myc translocus showed different V(H)DJ(H) rearrangement in almost all tumors without any alterations of the distance between c-myc and the IgH intron enhancer. This mouse model can be used for the in vivo analysis of c-myc deregulation and the tumor formation capacity of the IgH locus in aberrant rearrangements.