Abstract
Purpose: To generate a chondrocyte-specific deleter which can be visualised in vivo. We needed an improvement on the collagen type II which is significantly reduced in adult articular cartilage and expresses in kidney during development Methods: We have utilized a transgenic approach where we have used the human aggrecan enhancer/promoter to drive inducible Cre recombinase (Cre-ERT2) followed by an IRES luciferase forming a bicistronic mRNA in transgenic mice. Results: The expression and efficiency of the inducible cre recombinase was tested by examining X-gal staining of tissues from embryos as well as adult in double transgenic with Rosa 26R mice. Cre recombinase was induced by tamoxifen, at different time points during development and postnatally. X-gal staining was observed in growth plate and articular cartilage as well as the fibrocartilage of meniscus, trachea, and intervertebral discs reproducing the pattern of endogenous aggrecan gene expression. In addition to this mouse being an efficient deleter, the presence of luciferase allows the visualization of aggrecan expression in vivo. This has been tested before or after the induction of osteoarthritis through destabilisation of the medial meniscus ligament up to eight weeks post surgery. Conclusions: The aggrecan-CreERT2 will help us determine genes involvement in the integrity of the cartilage and visualize this complex in osteoarthritis
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