ASSEMBLY OF CARTILAGE COLLAGEN FIBRILS IS DISRUPTED BY OVEREXPRESSIONOF NORMAL TYPE-II COLLAGEN IN TRANSGENIC MICE

Cartilage collagen fibrils, which are characterized by their thin, uni form diameters, are formed of a multicomponent system of three collage n types (II, IX, and XI) and interacting proteoglycans. We have used a genetic approach to test whether the proper assembly of this multipro tein structure was altered by overexpression of one of its normal comp onents. Here we show that in transgenic mice in which the normal mouse alpha1(II) collagen is overexpressed, thick abnormal collagen fibrils are generated. Mice that showed the highest expression of the transge ne also displayed a larger proportion of abnormal fibrils and died at birth. We propose that an imbalance among the constituents of the cart ilage collagen fibrils disrupts the mechanism that controls their asse mbly. The results show the applicability of the transgenic mice system to studies of complex multicomponent protein assemblies in intact ani mals.