CRANIOFACIAL ABNORMALITIES IN MICE CARRYING A DOMINANT INTERFERENCE MUTATION IN TYPE-X COLLAGEN

Type X collagen is a short, non-fibril forming collagen restricted to hypertrophic cartilage, and has been hypothesized to play a role in en dochondral ossification. The purpose of the study was to investigate t he consequences resulting from the interference of type X collagen fun ction on the growth and development of the craniofacial skeleton throu gh analysis of transgenic mice with a dominant interference mutation f or type X collagen. The craniofacial tissues of al-day-old transgenic mice were examined by: cephalometric and radiographic densitometry ana lyses, conventional histology, and immunohistochemistry using antibodi es specific for either endogenous mouse type X collagen or the transge ne product. Genotypically positive mutant mice showed moderate but sta tistically significant craniofacial skeletal abnormalities, including the underdevelopment of the chondrocranium and mandible, but no cleft palate. Mean radiographic optical densities of the mutant condylar car tilage and the subchondylar areas were 32% less than the corresponding areas of normal mandibles, while mean radiographic optical density me asured at the incisor tooth point remained constant. Histologically, t ransgene-positive mice revealed compressed hypertrophic cartilage zone s and reduced trabeculae in both the mandibular condyle and the syncho ndroses of the chondrocranium. In the normal condyle, mouse type X col lagen was localized by the monospecific antibody against a synthetic r at type X collagen NC1 peptide throughout the hypertrophic cartilage l ayer; in the mutant condyle, immunoreactivity to endogenous type X col lagen was only seen sporadically. The truncated type X collagen transg ene product, identified with the monoclonal antibody against an epitop e within the chick type X collagen NC2 domain, persisted in the lower hypertrophic cartilage layer and the primary spongiosa, rather than be ing removed by subsequent endochondral ossification. The data suggeste d that the expression of the chick type X collagen transgene product w as strongly associated with the craniofacial skeletal abnormalities th at were distinct from other cartilage-related phenotypes. (C) 1997 Wil ey-Liss, Inc.