Construction of a model mouse library related to osteogenic and chondrogenic disease using an exchangeable gene trap mutagenesis

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Gene trapping in ES cells is a proven method for large-scale random insertional mutagenesis in the mouse genome. We have established an exchangeable gene trap system, in which a reporter gene can be exchanged for any other DNA of interest through Cre/mutant lox-mediated recombination. We isolated trap clones, analyzed trapped genes, and constructed the database for Exchangeable Gene Trap Clones (EGTC) [http://egtc.jp]. The EGTC database is the most extensive academic resource for gene-trap mouse lines. The number of registered ES cell lines was 1200 on March 2014. We also established 450 mouse lines from trap ES clones and deposited them in the mouse embryo bank at the CARD, Kumamoto Univ., Japan. Using EGTC database, we established 45 mouse lines related to osteogenic and chondrogenic metabolism. We analyzed the bone and cartilage phenotypes using micro CT, bone morphometry, biomechanical analyses, realtime-PCR, etc. Thirty seven mouse lines showed some bone and/or cartilage disorder.