Zp3-cre, a transgenic mouse line for the activation or inactivation of loxP-flanked target genes specifically in the female germ line
Zp3-cre, a transgenic mouse line for the activation or inactivation of loxP-flanked target genes specifically in the female germ line
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DOI：
10.1016/s0960-9822(06)00059-5
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发表时间：
1997-02-01
期刊：
影响因子：
9.2
通讯作者：
Martin, GR
中科院分区：
文献类型：
--
作者：
Lewandoski, M;Wassarman, KM;Martin, GR
位点特异性DNA重组酶Cre正被用于开发新一代控制小鼠基因表达的工具[1]。Cre介导两个直接重复的靶（loxP）位点重组为单个loxP位点，同时切除侧翼为loxP位点的DNA片段（“floxed”DNA）。这种重组可以通过切除阻断表达的弯曲DNA片段来激活基因，因为它分离了基因的调控和编码序列[2]或中断了基因的开放阅读框架。相反，如果基因的一个重要片段被弯曲，DNA切除可以使基因断裂[3]。体内基因激活或失活可以通过交配两只不同的动物来实现，一只携带具有适当放置的loxP位点的“靶基因”，另一只携带cre转基因。在大多数情况下，系统的特异性取决于ore表达的严格调控。我们在此描述了一种小鼠品系，其中ORE的表达受来自小鼠透明质酸3（Zp 3）基因的调控序列控制，该基因通常仅在第一次减数分裂完成之前在生长的卵母细胞中表达[4]。我们表明，在携带靶点的Zp 3-cre小鼠中，Cre介导的靶基因重组明显发生在100%的卵母细胞中。此外，在大多数携带靶点的Zp 3-cre小鼠的体细胞组织中未检测到Cre活性。这种鼠标线的潜在用途进行了讨论。
The site-specific DNA recombinase Cre is being used to develop a new generation of tools for controlling gene expression in mice [1]. Cre mediates the recombination of two directly repeated target (loxP) sites to a single loxP site, with concomitant excision of the DNA segment flanked by the loxP sites (the 'floxed' DNA). Such recombination can function to activate a gene by excising a flexed DNA segment that blocks expression because it either separates the regulatory and coding sequences of the gene [2] or interrupts the gene's open reading frame. Conversely, DNA excision can inactivate a gene if an essential fragment of the gene is flexed [3]. Gene activation or inactivation in vivo can be achieved by mating two different animals, one carrying a 'target gene' with appropriately placed loxP sites and one carrying a cre transgene. In most cases, the specificity of the system is dependent upon stringent regulation of ore expression. We describe here a mouse line in which ore expression is controlled by regulatory sequences from the mouse zona pellucida 3 (Zp3) gene, which is normally expressed exclusively in the growing oocyte prior to the completion of the first meiotic division [4]. We show that in target-bearing Zp3-cre mice, Cre-mediated recombination of the target gene apparently occurs in 100 % of oocytes. Moreover, Cre activity is not detected in the somatic tissues of most target-bearing Zp3-cre mice. Potential uses for this mouse line are discussed.