Towards a mutant map of the mouse--new models of neurological, behavioural, deafness, bone, renal and blood disorders.
Rastan S., Hough T., Kierman A., Hardisty R., Erven A., Gray IC., Voeling S., Isaacs A., Tsai H., Strivens M., Washbourne R., Thornton C., Greenaway S., Hewitt M., McCormick S., Selley R., Wells C., Tymowska-Lalanne Z., Roby P., Mburu P., Rogers D., Hagan J., Reavill C., Davies K., Glenister P., Fisher EMC., Martin J., Vizor L., Bouzyk M., Kelsell D., Guenet JL., Steel KP., Sheardown S., Spurr N., Gray I., Peters J., Nolan PM., Hunter AJ., Brown SDM.
With the completion of the first draft of the human genome sequence, the next major challenge is assigning function to genes. One approach is genome-wide random chemical mutagenesis, followed by screening for mutant phenotypes of interest and subsequent mapping and identification of the mutated genes in question. We (a consortium made up of GlaxoSmithKline, the MRC Mammalian Genetics Unit and Mouse Genome Centre, Harwell, Imperial College, London, and the Royal London Hospital) have used ENU mutagenesis in the mouse for the rapid generation of novel mutant phenotypes for use as animal models of human disease and for gene function assignment (Nolan et al., 2000). As of 2003, 35,000 mice have been produced to date in a genome-wide screen for dominant mutations and screened using a variety of screening protocols. Nearly 200 mutants have been confirmed as heritable and added to the mouse mutant catalogue and, overall, we can extrapolate that we have recovered over 700 mutants from the screening programme. For further information on the project and details of the data, see http://www.mgu.har.mrc.ac.uk/mutabase.