Transgenic mice with hematopoietic and lymphoid specific expression of Cre

Transgenic mice with hematopoietic and lymphoid specific expression of Cre
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DOI:
10.1002/immu.200310005
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发表时间:
2003-02-01
影响因子:
5.4
通讯作者:
Kioussis, D
Kioussis, D
中科院分区:
医学3区
文献类型:
--
作者:
de Boer, J;Williams, A;Kioussis, D

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基于噬菌体P1 Cre/IoxP的系统可用于在体内和体外操纵小鼠的基因组,从而允许产生组织特异性条件突变体。我们已经产生了使用vav调控元件在造血组织中表达Cre重组酶的小鼠品系,或者使用hCD 2启动子和基因座控制区(LCR)在淋巴细胞中表达Cre重组酶的小鼠品系。使用R26 R-EYFP Cre报告基因小鼠系来确定每个系中Cre表达的模式,并且使得能够在单细胞水平上评估Cre活性。分析表明,vav启动子元件能够直接在造血系统的所有细胞中的Cre介导的重组。另一方面,hCD 2启动子和LCR能够仅在T细胞和B细胞中驱动Cre介导的重组,但在其他造血细胞类型中不能。此外,在适当的组织中,floxed靶标的缺失在所有细胞中都是完全的,从而排除了Cre转基因多样化表达的可能性。这两种Cre转基因系都可用于在造血或淋巴组织的所有细胞内产生组织特异性基因缺失。
Bacteriophage P1 Cre/IoxP based systems can be used to manipulate the genomes of mice in vivo and in vitro, allowing the generation of tissue-specific conditional mutants. We have generated mouse lines expressing Cre recombinase in hematopoietic tissues using the vav regulatory elements, or in lymphoid cells using the hCD2 promoter and locus control region (LCR). The R26R-EYFP Cre reporter mouse line was used to determine the pattern of Cre expression in each line and enabled the assessment of Cre activity at a single-cell level. Analysis showed that the vav promoter elements were able to direct Cre-mediated recombination in all cells of the hematopoietic system. The hCD2 promoter and LCR on the other hand were able to drive Cre-mediated recombination only in T cells and B cells, but not in other hematopoietic cell types. Furthermore, in the appropriate tissues, deletion of the floxed target was complete in all cells, thereby excluding the possibility of variegated expression of the Cre transgene. Both of these Cre-transgenic lines will be useful in generating tissue-specific gene deletions within all the cells of hematopoietic or lymphoid tissues.