TARGETED MUTATION IN THE COL5A2 GENE REVEALS A REGULATORY ROLE FOR TYPE-V COLLAGEN DURING MATRIX ASSEMBLY

The tissue-specific organization of collagen molecules into tridimensi onal macroaggregates determines the physiomechanical properties of mos t connective tissues, but the factors and mechanisms controlling this process are unknown. It has been postulated that quantitatively minor types V and XI collagen regulate the growth of type I and II collagen fibrils, respectively. To test this hypothesis, we created mice that p roduce a structurally abnormal alpha 2(V) collagen chain. Homozygous m utant mice survive poorly, possibly because of complications from spin al deformities, and exhibit skin and eye abnormalities caused by disor ganized type I collagen fibrils. Our results demonstrate that type V c ollagen is a key determinant in the assembly of tissue-specific matric es, and provide an animal model for human connective tissue disorders.