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.
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