title: A dominant interference collagen X mutation disrupts hypertrophic chondrocyte pericellular matrix and glycosaminoglycan and proteoglycan distribution in transgenic mice.
abstract: Collagen X transgenic (Tg) mice displayed skeleto-hematopoietic defects in tissues derived by endochondral skeletogenesis.(1) Here we demonstrate that co-expression of the transgene product containing truncated chicken collagen X with full-length mouse collagen X in a cell-free translation system yielded chicken-mouse hybrid trimers and truncated chicken homotrimers; this indicated that the mutant could assemble with endogenous collagen X and thus had potential for dominant interference. Moreover, species-specific collagen X antibodies co-localized the transgene product with endogenous collagen X to hypertrophic cartilage in growth plates and ossification centers; proliferative chondrocytes also stained diffusely. Electron microscopy revealed a disrupted hexagonal lattice network in the hypertrophic chondrocyte pericellular matrix in Tg growth plates, as well as altered mineral deposition. Ruthenium hexamine trichloride-positive aggregates, likely glycosaminoglycans (GAGs)/proteoglycans (PGs), were also dispersed throughout the chondro-osseous junction. These defects likely resulted from transgene co-localization and dominant interference with endogenous collagen X. Moreover, altered GAG/PG distribution in growth plates of both collagen X Tg and null mice was confirmed by a paucity of staining for hyaluronan and heparan sulfate PG. A provocative hypothesis links the disruption of the collagen X pericellular network and GAG/PG decompartmentalization to the potential locus for hematopoietic failure in the collagen X mice.
authors.affiliation: Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania 19104-6046, USA. jecenko@vet.upenn.edu
authors.forename: O
authors.initials: O
authors.lastname: Jacenko
authors.forename: D
authors.initials: D
authors.lastname: Chan
authors.forename: A
authors.initials: A
authors.lastname: Franklin
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: C B
authors.initials: CB
authors.lastname: Underhill
authors.forename: J F
authors.initials: JF
authors.lastname: Bateman
authors.forename: M R
authors.initials: MR
authors.lastname: Campbell
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology; D002356:Cartilage / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002645:Chickens; D019902:Chondrocytes / Q000378:metabolism*; D024121:Collagen Type X / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D015870:Gene Expression; D005838:Genotype; D006025:Glycosaminoglycans / Q000378:metabolism*; D006132:Growth Plate / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009154:Mutation; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism*; D013997:Time Factors; D019076:Transgenes / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D024121:Collagen Type X; D006025:Glycosaminoglycans; D011509:Proteoglycans