The sophistication of genetic tools and the relative ease of breeding and housing mean that the mouse is the most widely used mammalian organism for basic and biomedical research. The genotype-phenotype information that will emerge from the efforts of the International Mouse Phenotyping Consortium (IMPC), now well into its first year, will advance all areas of the biological sciences, from behaviour to drug discovery, oncology to developmental biology.
The IMPC is one of the largest model-organism-based initiatives ever funded. Its aim is to generate and comprehensively characterise the phenotypes of viable knockouts for every gene in the mouse genome, and to compile the information in a public database (Brown & Moore, 2012). In practical terms, this means creating ~20,000 viable mouse lines and phenotyping them using dozens of tests, a feat that will be carried out through the coordinated efforts of several institutes in nine different countries. Moreover, the ~30% of knockouts that are expected to show embryonic lethality will be characterised, where possible, using specialised tests performed during embryonic development. The number and sophistication of tests used for phenotyping will likely increase as the protocols are refined and improved, and as notable mouse strains are selected for specialised phenotyping in secondary screens. For example, histopathology – the analysis of disease correlates through microscopic examination of tissues obtained from necropsy or biopsy – provides invaluable information that is complementary to in vivo assays, but it can currently only be performed on selected lines owing to economical and logistical constraints (Schofield et al., 2012).
The resources that will be generated by the IMPC include free access to all knockout mouse lines (or sperm) and a comprehensive database of corresponding phenotype information. These resources generated will be of value to investigators at all levels, and in many disciplines, from undergraduates to group leaders, basic scientists to clinicians.
Brown, S. D. M. and Moore, M. Towards an encyclopaedia of mammalian gene function: the International Mouse Phenotyping Consortium. (2012). Dis. Model. Mech. 5, 289-292.
Schofield P. N., Vogel, P., Gkoutos G. V., Sundberg, J. P. (2012). Exploring the elephant: histopathology in high-throughput phenotyping of mutant mice. Dis. Model. Mech. 5, 19-25.
Straight talk with… Steve Brown. Interview by Hannah Waters. (2011). Nat. Med. 17, 1332.
January 2012 DMM Podcast: Paul Schofield on histopathology in high-throughput phenotyping of mutant mice.
IMPC website: http://www.mousephenotype.org/