AN INBRED LINE OF TRANSGENIC MICE EXPRESSING AN INTERNALLY DELETED GENE FOR TYPE-II PROCOLLAGEN (COL2A1) - YOUNG MICE HAVE A VARIABLE PHENOTYPE OF A CHONDRODYSPLASIA AND OLDER MICE HAVE OSTEOARTHRITIC CHANGES IN JOINTS

Studies were carried out on a line of transgenic mice that expressed a n internally deleted COL2A1 gene and developed a phenotype resembling human chondrodysplasias (Vandenberg et al. 1991. Proc. Natl. Acad. Sci . USA. 88:7640-7644. Marked differences in phenotype were observed wit h propagation of the mutated gene in an inbred strain of mice in that approximately 15% of the transgenic mice had a cleft palate and a leth al phenotype, whereas the remaining mice were difficult to distinguish from normal littermates. 1-d- and 3-mo-old transgenic mice that were viable showed microscopic signs of chondrodysplasia with reduced amoun ts of collagen fibrils in the cartilage matrix, dilatation of the roug h surfaced endoplasmic reticulum in the chondrocytes, and decrease of optical path difference in polarized light microscopy. The transgenic mice also showed signs of disturbed growth as evidenced by lower body weight, lower length and weight of the femur, decreased bone collagen, decreased bone mineral, and decreased resistance of bone to breakage. Comparisons of mice ranging in age from 1 d to 15 mo demonstrated tha t there was decreasing evidence of a chondrodysplasia as the mice grew older. Instead, the most striking feature in the 15-mo-old mice were degenerative changes of articular cartilage similar to osteoarthritis.