Conditional and inducible gene recombineering in the mouse inner ear
Conditional and inducible gene recombineering in the mouse inner ear
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DOI：
10.1016/j.brainres.2006.01.040
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发表时间：
2006-05-26
期刊：
影响因子：
2.9
通讯作者：
Beisel, Kirk W.
中科院分区：
文献类型：
--
作者：
Tian, Yong;James, Sally;Beisel, Kirk W.
基因工程小鼠极大地提高了我们对基因功能和疾病机制的理解。然而，传统的敲除方法在突变体的总体生存力方面具有局限性。Cre/loxP系统在内耳中的应用可以通过产生条件基因重组工程来帮助绕过这一困难。然而，要做到这一点，需要一个表达系统，允许耳朵特异性的时间诱导，基因废除一个或多个日益可用的floxed基因。迄今为止，三种方法已成功地用于创建小鼠内耳特异性Cre系：常规转基因、BAC转基因和基因敲入。不幸的是，条件性Cre活性的时间并不超出控制Cre表达的基因的调控范围。纠正这个问题需要在内耳中产生他莫昔芬或四环素诱导系统。检测整合酶在不同位点的表达将有助于外源转基因表达的研究。小鼠基因组的这些遗传应用将极大地推进体内基因功能研究。(c)2006 Elsevier B. V.保留所有权利。
Genetically engineered mice have greatly improved our understanding of gene functions and disease mechanisms. Nevertheless, the traditional knock-out approach has limitations in the overall viability of mutants. The application of the Cre/loxP system in the inner ear can help bypass this difficulty by generation of conditional gene recombineering. However, to do so requires an expression system that allows ear-specific temporally inducible, gene abrogation of one or more of the increasingly available floxed genes. To date, three approaches have been successfully used to create murine inner ear-specific Cre lines: conventional transgenesis, BAC transgenesis, and gene knock-in. Unfortunately, timing of conditional Cre activity does not extend beyond the regulatory range of the gene controlling Cre expression. Rectification of this problem requires the generation of tamoxifen or tetracycline inducible systems in the inner ear. Examination of integrase expression at different loci will facilitate studies on the expression of exogenous transgenes. These genetic applications for the mouse genome will dramatically advance in vivo gene function studies. (c) 2006 Elsevier B.V. All rights reserved.