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To define IGF-I/IGF-IR actions in chondrocytes, cartilage-specific IGF-IR KO mouse models ( cart IGF-IR / mice) were made by crossing floxed IGF-IR mice that carried loxP sequences flanking the exon 3 of the gene (30) with mice expressing Cre recombinase transgene, under the control of a type II collagen promoter (31)