Inter-chromosomal recombination of Mll and Af9 genes mediated by cre-loxP in mouse development
Inter-chromosomal recombination of Mll and Af9 genes mediated by cre-loxP in mouse development
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DOI：
10.1093/embo-reports/kvd021
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发表时间：
2000-08-01
期刊：
影响因子：
7.7
通讯作者：
Rabbitts, TH
中科院分区：
文献类型：
--
作者：
Collins, EC;Pannell, R;Rabbitts, TH
染色体易位是许多白血病、淋巴瘤和肉瘤的病因学中的关键事件，导致癌基因表达增强或产生新的融合基因。研究这些事件的生物学结果理想地需要重演染色体易位本身的组织特异性和时间。我们已经使用噬菌体P1的Cre-loxP系统在小鼠发育期间诱导从头M11-Af 9染色体重组。将loxP位点分别引入染色体9和4上的Mll和Af 9基因中，并将携带这些等位基因的小鼠与表达Cre重组酶的小鼠杂交。检测到产生的Mll-Af 9融合基因，其转录和剪接得到验证。因此，可以在小鼠中实现程序性染色体间重组。这种方法应该允许设计的小鼠模型的肿瘤发生具有更大的生物相关性比目前可用的。
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.