Resources to functionally test mouse genes are nearing completion but others lag behind. Credit: Katie Vicari

Thanks to sequencing and annotation efforts, we now know the sequence of next to all mouse genes. What we are lacking is a comprehensive understanding of what these 20,000 genes actually do. Because a task of this magnitude cannot be tackled in piecemeal fashion, several years ago the mouse community started large-scale efforts, brought together under the umbrella of the International Knockout Mouse Consortium. Its goal is to mutate every protein-coding gene in an inbred mouse strain, C57BL/6, and to make the vectors to do so, as well as the resulting embryonic stem cells and mouse strains, available to the community. Although this work is ongoing, 2011 marked a considerable expansion of these tools. Researchers at the Wellcome Trust Sanger Institute led an effort to create conditional knockout alleles that can be switched back to wild type and subsequently selectively knocked out in a tissue-specific or time-specific manner (Nature 474, 337–342; 2011). This resource currently encompasses roughly half of all mouse genes, with a pipeline set up to tackle the other half. Notably, a large percentage of the C57BL/6N embryonic stem cells with these conditional alleles are germline-competent and mice carrying them can thus be bred easily and are ready for phenotyping. Consortia such as The European Mouse Disease Clinic apply standardized phenotypic tests to various mouse strains generated by their partners at the International Knockout Mouse Consortium. Before long the (inbred) mouse will be in the fortunate position of having functional data on each of its genes. The rat will be next, with the Knock Out Rat Consortium following in the footsteps of the International Knockout Mouse Consortium.