Buchholz F, Refaeli Y, Trumpp A, Bishop J M
Hooper Research Foundation, University of California San Francisco, 94143-0552, USA.
EMBO Rep. 2000 Aug;1(2):133-9. doi: 10.1093/embo-reports/kvd027.
Transgenic mice have been used to explore the role of chromosomal translocations in the genesis of tumors. But none of these efforts has actually involved induction of a translocation in vivo. Here we report the use of Cre recombinase to replicate in vivo the t(8;21) translocation found in human acute myeloid leukemia (AML). As in the human tumors, the murine translocation fuses the genes AML1 and ETO. We used homologous recombination to place loxP sites at loci that were syntenic with the break points for the human translocation. Cre activity was provided in mice by a transgene under the control of the Nestin promoter, or in cultured B cells by infecting with a retroviral vector encoding Cre. In both instances, Cre activity mediated interchromosomal translocations that fused the AML1 and ETO genes. Thus, reciprocal chromosomal translocations that closely resemble rearrangements found in human cancers can be achieved in mice.
转基因小鼠已被用于探究染色体易位在肿瘤发生中的作用。但这些研究均未在体内实际诱导出易位。在此，我们报告利用Cre重组酶在体内复制人类急性髓系白血病（AML）中发现的t(8;21)易位。与人类肿瘤一样，小鼠的这种易位使AML1和ETO基因融合。我们利用同源重组将loxP位点置于与人类易位断点同线性的位点。通过巢蛋白启动子控制的转基因在小鼠中提供Cre活性，或通过用编码Cre的逆转录病毒载体感染培养的B细胞来提供Cre活性。在这两种情况下，Cre活性介导了使AML1和ETO基因融合的染色体间易位。因此，在小鼠中可以实现与人类癌症中发现的重排极为相似的相互染色体易位。
