Fig. 1: Rapid-throughput joint phenotyping identifies osteoarthritis genes.

Knee joints from randomly selected 16-week-old mutant mice generated at the Wellcome Trust Sanger Institute (WTSI) for the International Mouse Phenotyping Consortium (IMPC) are analyzed by three imaging modalities; iodine contrast-enhanced micro-computerized tomography (ICEμCT), joint surface replication (JSR) and subchondral bone X-ray microradiography (scXRM). The methods were validated by comparison with scoring of histological sections (Osteoarthritis Research Society International (OARSI) histology after destabilization of the medial meniscus (DMM) provocation surgery). Twenty-five mouse lines (three-way Venn diagram) had outlier phenotypes relative to wild-type reference data following statistical analyses. Further prioritization was based on additional skeletal abnormalities identified in mutant mice, gene expression, association with human disease and literature searching. Boxes and four-way Venn diagram show top-ranked genes in each category. Pitx1, Bhlhe40, Sh3bp4, and Unk were the top-ranked genes. Green text: most severely abnormal joint phenotypes. Red boxes indicate mutant lines with increased articular cartilage surface damage. Source data are provided as a Source Data file.