Novel models of late onset, progressive osteoarthritis caused by point mutations in the two alpha chains of collagen type I

Genetic modification is a useful tool for identifying novel genes associated with osteoarthritis (OA) and we have combined a phenotype-driven screen with ageing to identify mutations resulting in late-onset or age-related disease. As part of the Harwell Ageing Screen mutagenised mice were aged to 18 months and phenotyped at various time points, to allow for detection of late onset disease and to track its progression. This approach has identified 2 novel models of late onset, progressive OA, caused by point mutations in the genes Col1a2 or Col1a1. Defects in the alpha subunits of Collagen I are most notably associated with osteogenesis imperfecta (OI) and Ehlers Danlos syndrome, although there has been an association found between Col1a2 and OA in a founder population (Snelgrove et al, 2005). Our current work seeks to examine the causation between Collagen I defects and OA.