A dominant interference collagen X mutation disrupts hypertrophic chondrocyte pericellular matrix and glycosaminoglycan and proteoglycan distributionin transgenic mice

Collagen X transgenic (Tg) mice displayed skeleto-hematopoictic defects in tissues derived by endochondral skeletogenesis.' Here we demonstrate that c o-expression of the transgene product containing truncated chicken collagen X with full-length mouse collagen X in a cell-free translation system yiel ded chicken-mouse hybrid trimers and truncated chicken homotrimers; this in dicated that the mutant could assemble with endogenous collagen X and thus had potential for dominant interference. Moreover, species-specific collage n X antibodies co-localized the transgene product with endogenous collagen X to hypertrophic cartilage in growth plates and ossification centers; prol iferative chondrocytes also stained diffusely. Electron microscopy revealed a disrupted hexagonal lattice network in the hypertrophic chondrocyte peri cellular matrix in Tg growth plates, as well as altered mineral deposition. Ruthenium hexamine trichloride-positive aggregates, likely glycosaminoglyc ans (GAGs)/proteoglycans (PGs), were also dispersed throughout the chondro- osseous junction. These defects likely resulted from transgene co-localizat ion and dominant interference with endogenous collagen X. Moreover, altered GAG/PG distribution in growth plates of both collagen X Tg and null mice w as confirmed by a paucity of staining for hyaluronan and heparan sulfate PG . A provocative hypothesis links the disruption of the collagen X pericellu lar network and GAG/PG decompartmentalization to the potential locus for he matopoietic failure in the collagen X mice.