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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。

相似文献

1
Comprehensive mammalian genetics: history and future prospects of gene trapping in the mouse.哺乳动物综合遗传学:小鼠基因捕获的历史与未来前景
Int J Dev Biol. 1998;42(7):1025-36.
2
Disruption and sequence identification of 2,000 genes in mouse embryonic stem cells.对小鼠胚胎干细胞中2000个基因的破坏与序列鉴定。
Nature. 1998 Apr 9;392(6676):608-11. doi: 10.1038/33423.
3
The gene trap resource: a treasure trove for hemopoiesis research.基因捕获资源:造血研究的宝库。
Exp Hematol. 2005 Aug;33(8):845-56. doi: 10.1016/j.exphem.2005.03.016.
4
Gene trapping in embryonic stem cells.胚胎干细胞中的基因捕获
Methods Enzymol. 2006;420:136-62. doi: 10.1016/S0076-6879(06)20008-9.
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Gene trap mutagenesis: a functional genomics approach towards reproductive research.基因捕获诱变:一种用于生殖研究的功能基因组学方法。
Mol Hum Reprod. 2007 Nov;13(11):771-9. doi: 10.1093/molehr/gam069. Epub 2007 Sep 23.
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High-throughput trapping of secretory pathway genes in mouse embryonic stem cells.小鼠胚胎干细胞中分泌途径基因的高通量捕获
Nucleic Acids Res. 2006 Feb 13;34(3):e25. doi: 10.1093/nar/gnj026.
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Functional genomics in mice by tagged sequence mutagenesis.通过标签序列诱变进行小鼠功能基因组学研究。
Nat Genet. 1997 Aug;16(4):338-44. doi: 10.1038/ng0897-338.
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Gene-trap mutagenesis: past, present and beyond.基因捕获诱变:过去、现在及未来。
Nat Rev Genet. 2001 Oct;2(10):756-68. doi: 10.1038/35093548.
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Suppression of nonsense-mediated mRNA decay permits unbiased gene trapping in mouse embryonic stem cells.抑制无义介导的mRNA降解可在小鼠胚胎干细胞中实现无偏倚的基因捕获。
Nucleic Acids Res. 2005 Feb 1;33(2):e20. doi: 10.1093/nar/gni022.
10
The Centre for Modeling Human Disease Gene Trap resource.人类疾病基因陷阱资源建模中心。
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D557-9. doi: 10.1093/nar/gkh106.

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