OSTEOCHONDRODYSPLASIA OCCURRING IN TRANSGENIC MICE EXPRESSING INTERFERON-GAMMA

In addition to various biological activities, interferon-gamma (IFN-ga mma) inhibits bone resorption and collagen synthesis. We produced a tr ansgenic mouse line expressing the murine IFN-gamma gene and protein i n the bone marrow and thymus. Forty-five transgenic FVB/NCr mice, 23 d ays-9 months of age, were studied for anomalies in the skeletal system . The transgenic mice had short, wide, and deformed long bones. Young transgenic mice had epiphyseal plates severely thickened with zones of hypertrophy and degeneration with irregular metaphyseal borders. Cart ilagenous masses were also observed in the metadiaphyseal marrow cavit ies. These lesions were primarily seen in long bones and ribs. Adult t ransgenic mice had residues of degenerated cartilagenous masses in the diaphyses. Many osteoclasts with well-developed ruffled borders were present on the metaphyseal cartilagenous masses in young transgenic mi ce. Adult transgenic mice had less prominent primary spongiosa with fe wer osteoclasts at the metaphysis as compared with nontransgenic contr ols. The cortical bones of the transgenic mice were thinner and more i mmature compared with controls. Transgenic mice also had fractures, di sruption of the epiphyseal plate, and degeneration of articular cartil age. Thus, the IFN-gamma transgenic mice developed a complex chondro-o sseous lesion that was diagnosed as osteochondrodysplasia. The lesions may originate from primarily decreased matrix synthesis in bone and c artilage and also possible osteoclast-related changes caused by IFN-ga mma overexpression in the bone marrow. Our IFN-gamma transgenic mouse will be a useful model to investigate the role of IFN-gamma in bone me tabolism.