Collins E C, Pannell R, Simpson E M, Forster A, Rabbitts T H
MRC Laboratory of Molecular Biology, Cambridge, UK.
EMBO Rep. 2000 Aug;1(2):127-32. doi: 10.1093/embo-reports/kvd021.
Chromosomal translocations are crucial events in the aetiology of many leukaemias, lymphomas and sarcomas, resulting in enforced oncogene expression or the creation of novel fusion genes. The study of the biological outcome of such events ideally requires recapitulation of the tissue specificity and timing of the chromosomal translocation itself. We have used the Cre-loxP system of phage P1 to induce de novo Mll-Af9 chromosomal recombination during mouse development. loxP sites were introduced into the Mll and Af9 genes on chromosomes 9 and 4, respectively, and mice carrying these alleles were crossed with mice expressing Cre recombinase. A resulting Mll-Af9 fusion gene was detected whose transcription and splicing were verified. Thus, programmed interchromosomal recombination can be achieved in mice. This approach should allow the design of mouse models of tumorigenesis with greater biological relevance than those available at present.
染色体易位是许多白血病、淋巴瘤和肉瘤病因中的关键事件，会导致癌基因的强制表达或新融合基因的产生。对这类事件的生物学结果进行研究，理想情况下需要重现染色体易位本身的组织特异性和发生时间。我们利用噬菌体P1的Cre-loxP系统在小鼠发育过程中诱导产生新的Mll-Af9染色体重组。分别将loxP位点引入9号和4号染色体上的Mll和Af9基因，携带这些等位基因的小鼠与表达Cre重组酶的小鼠杂交。检测到一个产生的Mll-Af9融合基因，其转录和剪接得到了验证。因此，可在小鼠中实现程序性染色体间重组。这种方法应能设计出比目前可用模型具有更高生物学相关性的肿瘤发生小鼠模型。
