International Mouse Phenotyping Consortium (IMPC) 2019

Goals of the IMPC www.mousephenotype.org Building the first truly comprehensive, functional catalogue of a mammalian genome. Systematically phenotyping 20,000 knockout mouse strains, one for each gene. Our current database has: Over 6000 genes phenotyped (and growing!) All data freely available to the scientific community. Mutant strains available to order for your own research. www.mousephenotype.org Creating a comprehensive catalogue of mammalian gene function.

Major achievements of the IMPC Discovered extensive pleiotropy and sexual dimorphism. Deduced that one third of genes have embryo defects and are enriched for human disease genes. Created hundreds of novel mouse models of human disease, based on phenotype match with clinical features. Published systemic analyses on Metabolism Eyesight Hearing More coming…. Male Greater No Sex Effect Female Greater Moore BA et al. Commun Biol. 2018 Dec 21;1:236. Top Left- The role of sex in explaining variation in phenotypes of wildtype mice as assessed using continuous data from the IMPC Top Right- Cdkn2a knockout mice had ocular lesions consistent with persistent tunica vasculosa lentis, with most severe cases having posterior lenticonus where the lens was adhered to the retina at the optic disc. https://www.nature.com/articles/s42003-018-0226-0 Bottom left- Links between unexplored metabolic genes and parameters that contribute to strong metabolic phenotypes in males https://www.nature.com/articles/s41467-017-01995-2 Bottom Right -Summary audiograms for the 67 hearing loss genes identified within the IMPC. ABR screen assessing auditory thresholds (dB SPL) at five frequencies—6, 12, 18, 24 and 30kHz. The genes are divided into four broad categories of hearing loss—severe (magenta lines), mild (orange lines), high frequency (green lines) and low frequency (blue lines). 10.1038/s41467-017-00595-4 Creating a comprehensive catalogue of mammalian gene function. Rozman J et al.Nat Commun. 2018 Jan 18;9(1):288 Bowl MR et al.Nat Commun. 2017 Oct 12;8(1):886

The IMPC’s expanding mission Our 10 year strategy document outlines our future plans, where we aim to: Continue to develop strategic partnerships with global genetic disease consortia. Complete a null mouse mutant resource for the coding genome Continue to push the state of the art in genomic engineering to create mouse models with human disease variants. Design and generate mouse strains that model variation in the non-coding genome. And much more…. Creating a comprehensive catalogue of mammalian gene function.