Assembly of cartilage collagen fibrils is disrupted by overexpression of normal type II collagen in transgenic mice.

Cartilage collagen fibrils, which are characterized by their thin, uniform diameters, are formed of a multicomponent system of three collagen types (II, IX, and XI) and interacting proteoglycans. We have used a genetic approach to test whether the proper assembly of this multiprotein structure was altered by overexpression of one of its normal components. Here we show that in transgenic mice in which the normal mouse alpha 1(II) collagen is overexpressed, thick abnormal collagen fibrils are generated. Mice that showed the highest expression of the transgene also displayed a larger proportion of abnormal fibrils and died at birth. We propose that an imbalance among the constituents of the cartilage collagen fibrils disrupts the mechanism that controls their assembly. The results show the applicability of the transgenic mice system to studies of complex multicomponent protein assemblies in intact animals. IMAGES:

以纤细均匀直径为特征的软骨胶原原纤维（cartilage collagen fibrils），由II、IX、XI型三种胶原以及相互作用的蛋白聚糖（proteoglycans）构成的多组分体系组装而成。本研究采用遗传学手段，探究该多蛋白结构的正常组装过程是否会因其中一种正常组分的过表达而受到干扰。研究结果显示，在正常小鼠α1(II)胶原（alpha 1(II) collagen）过表达的转基因小鼠（transgenic mice）中，会生成粗大的异常胶原原纤维。转基因表达水平最高的小鼠，其异常原纤维占比更高，且会在出生时死亡。我们推测，软骨胶原原纤维组分间的失衡会破坏调控其组装的分子机制。本研究结果证实，转基因小鼠系统可用于完整动物体内复杂多组分蛋白质组装的相关研究。图像：