Tian Yong, James Sally, Zuo Jian, Fritzsch Bernd, Beisel Kirk W
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Brain Res. 2006 May 26;1091(1):243-54. doi: 10.1016/j.brainres.2006.01.040. Epub 2006 Feb 20.
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.
基因工程小鼠极大地增进了我们对基因功能和疾病机制的理解。然而，传统的基因敲除方法在突变体的整体生存能力方面存在局限性。Cre/loxP系统在内耳中的应用可以通过产生条件性基因重组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，该系统能够允许在内耳中进行特定时间的诱导，对越来越多可用的loxP侧翼基因中的一个或多个进行基因敲除。迄今为止，已经成功地使用了三种方法来创建小鼠内耳特异性Cre系：传统转基因、BAC转基因和基因敲入。不幸的是，条件性Cre活性的时间范围并没有超出控制Cre表达的基因的调控范围。解决这个问题需要在内耳中产生他莫昔芬或四环素诱导系统。检查不同位点的整合酶表达将有助于对外源转基因表达的研究。这些针对小鼠基因组的遗传应用将极大地推动体内基因功能研究。
