Garofalo S, Metsäranta M, Ellard J, Smith C, Horton W, Vuorio E, de Crombrugghe B
Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Proc Natl Acad Sci U S A. 1993 May 1;90(9):3825-9. doi: 10.1073/pnas.90.9.3825.
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.
软骨胶原纤维的特点是直径细且均匀，由三种胶原蛋白类型（II、IX和XI）以及相互作用的蛋白聚糖组成的多组分系统形成。我们采用了一种遗传学方法来测试这种多蛋白结构的正确组装是否会因其中一种正常成分的过表达而改变。在此我们表明，在正常小鼠α1（II）胶原蛋白过表达的转基因小鼠中，会产生粗大的异常胶原纤维。转基因表达最高的小鼠也表现出更大比例的异常纤维，并在出生时死亡。我们提出，软骨胶原纤维成分之间的失衡会破坏控制其组装的机制。结果表明转基因小鼠系统适用于完整动物中复杂多组分蛋白质组装的研究。
