The knockout mouse project

Abstract

Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain.

Figure 1

Structure of resource production in the proposed KOMP. Using the mouse genome sequence as a foundation, knockout alleles in ES cells will be produced for all genes. A subset of ES cell knockouts will be used each year to produce knockout mice, determine the expression pattern of the targeted gene in a variety of tissues and carry out screening-level (Tier 1) phenotyping. In a subset of mouse lines, transcriptome analysis and more detailed system-specific (Tier 2) phenotyping will be done. Finally, specialized phenotyping will be done on a smaller number of mouse lines with particularly interesting phenotypes. All stages will occur within the purview of the KOMP except for the specialized phenotyping, which will occur in individual laboratories with particular expertise.