Now and future of mouse mutagenesis for human disease models
Now and future of mouse mutagenesis for human disease models
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DOI：
10.1016/s1673-8527(09)60076-x
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发表时间：
2010-09-01
影响因子：
5.9
通讯作者：
Gondo, Yoichi
中科院分区：
文献类型：
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作者：
Gondo, Yoichi
人类基因组计划的主要目标之一是了解基因和基因组的生物学功能，以及开发人类疾病的临床应用。为此，动物模型的实验验证和临床前试验是必不可少的。小鼠（Mus musculus）是最好的动物模型之一，因为遗传学在小鼠中得到了很好的建立，胚胎操作技术也得到了很好的发展。自1997年以来，已经进行了大规模的小鼠诱变项目，以开发各种小鼠模型。最初，用N-乙基-N-亚硝基脲（ENU）进行的表型驱动诱变是国际上的主要努力，随后是敲除/条件小鼠项目和基因驱动诱变。在开始时，简单的单基因性状在实验条件下已经阐明。然后，具有各种环境相互作用和基因间相互作用（上位性）的更复杂的性状已经受到突变小鼠的挑战。此外，染色体替代品系和协作杂交品系也可用于阐明小鼠的复杂性状。总之，具有诱变的小鼠模型和各种实验室品系将加速小鼠以及人类的功能基因组学研究。
One of the major objectives of the Human Genome Project is to understand the biological function of the gene and genome as well as to develop clinical applications for human diseases. For this purpose, the experimental validations and preclinical trails by using animal models are indispensable. The mouse (Mus musculus) is one of the best animal models because genetics is well established in the mouse and embryonic manipulation technologies are also well developed. Large-scale mouse mutagenesis projects have been conducted to develop various mouse models since 1997. Originally, the phenotype-driven mutagenesis with N-ethyl-N-nitrosourea (ENU) has been the major efforts internationally then knockout/conditional mouse projects and gene-driven mutagenesis have been following. At the beginning, simple monogenic traits in the experimental condition have been elucidated. Then, more complex traits with variety of environmental interactions and gene-to-gene interactions (epistasis) have been challenged with mutant mice. In addition, chromosomal substitution strains and collaborative cross strains are also available to elucidate the complex traits in the mouse. Altogether, mouse models with mutagenesis and various laboratory strains will accelerate the studies of functional genomics in the mouse as well as in human.