Generation of mouse mutants as a tool for functional genomics.

As sequence information becomes available from the Human Genome Project, key developments include systematic methods for assigning function to each of the 100,000 or so genes. Strategies for coping with this sequence information, including microarray analysis and proteomics, will further our understanding of how genes function and interact. Ultimately, however, the simplest way to understand how a gene works is to examine the consequences of interference with its function: mutational analysis. The mouse represents the model organism of choice in the analysis of gene function; close enough to human to represent a satisfactory model organism, yet relatively easy to manipulate at a genetic level. Two complementary approaches, genotype- and phenotype-based, have been established in the mouse genetics and genomics communities to systematically generate new mouse mutations. Genotype-based approaches are advantageous in that molecular analysis of mutations is facilitated. Phenotypic analysis, however, is often assumed based on gene expression patterns, often leading to unexpected results. Phenotype-based approaches do not make prior assumptions about gene function. Often, however, it may be difficult to define the underlying genetic lesion. Progress in each of these approaches will be considered and situations in which they might be mutually beneficial will be investigated.