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哺乳动物综合遗传学:小鼠基因捕获的历史与未来前景

Comprehensive mammalian genetics: history and future prospects of gene trapping in the mouse.

作者信息

Zambrowicz B P, Friedrich G A

机构信息

Lexicon Genetics, The Woodlands, Texas 77381, USA.

出版信息

Int J Dev Biol. 1998;42(7):1025-36.

PMID:9853834
Abstract

Gene trapping has matured into a tool with tremendous potential for mammalian biology. It both mutates and helps identify genes and can be streamlined so that many thousands of insertions can be characterized. In only a few years most of the genome of the mouse will be tagged and mutated using the latest gene trap designs. By creating such a resource, costly and time consuming alternative methods of mutagenesis and gene identification can be avoided allowing biologists to concentrate on determining gene function in vivo. This will mean a major shift in how the genome will be mined for new drug targets. Notably, gene discovery via gene traps does not suffer from the limitations of other methods as it is not biased by expression level. Mouse strains with specific gene mutations can be easily derived from a gene trap library constructed using embryonic stem cells. These strains will help determine the role of the gene product in mammalian physiology and hence the relevance of the gene product to human disease.

摘要

基因捕获已发展成为一种对哺乳动物生物学具有巨大潜力的工具。它既能使基因发生突变,又有助于识别基因,并且可以进行优化,从而能够对成千上万的插入进行表征。在短短几年内,利用最新的基因捕获设计,小鼠的大部分基因组将被标记和突变。通过创建这样一种资源,可以避免诱变和基因识别中成本高昂且耗时的替代方法,使生物学家能够专注于确定基因在体内的功能。这将意味着在挖掘基因组以寻找新的药物靶点的方式上发生重大转变。值得注意的是,通过基因捕获进行基因发现不受其他方法的限制,因为它不受表达水平的影响。具有特定基因突变的小鼠品系可以很容易地从使用胚胎干细胞构建的基因捕获文库中获得。这些品系将有助于确定基因产物在哺乳动物生理学中的作用,从而确定该基因产物与人类疾病的相关性。

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