Vitaterna Martha Hotz, Pinto Lawrence H, Takahashi Joseph S
Center for Functional Genomics and Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
Trends Neurosci. 2006 Apr;29(4):233-40. doi: 10.1016/j.tins.2006.02.006. Epub 2006 Mar 7.
Significant developments have occurred in our understanding of the mammalian genome thanks to informatics, expression profiling and sequencing of the human and rodent genomes. However, although these facets of genomic analysis are being addressed, analysis of in vivo gene function remains a formidable task. Evaluation of the phenotype of mutants provides powerful access to gene function, and this approach is particularly relevant to the nervous system and behavior. Here, we discuss the complementary mouse genetic approaches of gene-driven, targeted mutagenesis and phenotype-driven, chemical mutagenesis. We highlight an NIH-supported large-scale effort to use phenotype-driven mutagenesis screens to identify mouse mutants with neural and behavioral alterations. Such single-gene mutations can then be used for gene identification using positional candidate gene-cloning methods.
得益于信息学、人类和啮齿动物基因组的表达谱分析及测序技术，我们对哺乳动物基因组的认识取得了重大进展。然而，尽管基因组分析的这些方面已有进展，但对体内基因功能的分析仍然是一项艰巨的任务。对突变体表型的评估为了解基因功能提供了有力途径，这种方法在神经系统和行为研究中尤为重要。在此，我们讨论基因驱动的靶向诱变和表型驱动的化学诱变这两种互补的小鼠遗传学方法。我们着重介绍了一项由美国国立卫生研究院支持的大规模研究，该研究利用表型驱动的诱变筛选来鉴定具有神经和行为改变的小鼠突变体。然后，这些单基因突变可用于通过定位候选基因克隆方法进行基因鉴定。
