Abstract
In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed high-throughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research.
Highlights
Annotation of the human and mouse genomes has identified more than 20,000 protein-coding genes and more than 3,000 noncoding RNA genes
Despite the dramatic increase in knowledge of variation in human genomes of healthy and diseased individuals, the normal functions of common forms of most genes are still unknown and the disease significance of rare variants remains obscure as well. Mutation of those genes is required in model organisms
Conservation of most aspects of mammalian development, anatomy, metabolism, and physiology between humans and mice is underscored by strong one-to-one orthologous relationships between genes of the two species
Summary
Annotation of the human and mouse genomes has identified more than 20,000 protein-coding genes and more than 3,000 noncoding RNA genes. To deliver the ES cell resource toward this vision of functional annotation, four international programs in Europe and North America were established with the goal of achieving saturation mutagenesis of the mouse genome: EUCOMM, KOMP, NorCOMM, and TIGM (see Table 3). These programs were the founding members of the International Knockout Mouse Consortium (IKMC), fostering groups to work together in a highly coordinated, standardized manner, to share technologies, to maximize output, and to largely avoid duplication of effort (Collins et al 2007). The IKMC consortium has generated mainly conditional and constitutive mutations, with the former class of mutations facilitating tissue-specific assessment of gene function at desired time points, especially in situations where an essential requirement of a gene product in one context can exclude analysis in another
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