Zebrafish are a well-established model to study developmental biology and early physiology. Their optical translucency, genetic tractability and the availability of fluorescent reporter lines has been extensively used to give insights into cell behaviour, organogenesis and many disease states. However, they can also be used to model diseases associated with ageing. The degenerative joint disease osteoarthritis affects around 1 in 8 of the population worldwide. Wear and tear through joint use and genetic factors are known to play a role, yet we still know relatively little about the interplay between genes and mechanics in the early stages of disease pathology. Using genome editing we have generated 10 zebrafish lines carrying mutations in genes identified from human genome wide association studies (GWAS) as osteoarthritis susceptibility genes (runx2a, barx1, gdf5, col11a2, col9a1, dot1l, chsy1, ncoa3, wnt16 and mcfl2a). Using a range of techniques (e.g. histology, confocal of transgenic lines, second harmonic generation, micro computed tomography, functional analysis) we show that not only do these mutants develop osteoarthritis as they age but that most mutants show changes to cell behaviour, joint shape and joint function that are detectable early in development, by 5 days post fertilisation. Using Finite Element Analysis on wild type and mutant larval joints we have tested the relative impact of joint shape and of cartilage properties on skeletal strain and show that shape has a greater impact on joint performance. To facilitate high throughput screening of CRISPR mutants we have developed an automated 3D analysis tool to segment skeletal elements through which we can define alpha shape, volume and shape variation allowing us to group genes by their mutant phenotypes. I will also, briefly, discuss our plans to test the effects of altered gravitational fields on zebrafish joint physiology.