Abnormal craniofacial morphology and cartilage structure in transgenic mice harboring a Gly --> Cys mutation in the cartilage-specific type II collagen gene.

Gross morphology and histology of the craniofacial complex was studied in the offspring of two transgenic founder mice, Gly85-1 and Gly85-3, carrying several copies of a mouse type II collagen transgene that causes a single amino acid substitution (Gly-->Cys) at position 85 of the triple helix. The newborn transgenic mice had a short snout and mandible, a protruding tongue, a cleft of the secondary palate with the tongue situated between the shelves, and a doming cranial vault. Radiological examination revealed that the cranial base of the transgenic mice was shorter and its posterior part downward bent; in addition both the palate and the cribriform plate were less extended in relation to the cranial base than in the controls. Histologically the midline cartilaginous structures were composed of densely packed enlarged chondrocytes in a reduced extracellular matrix containing abnormally thick collagen fibrils. With the exception of the zone of hypertrophic chondrocytes the matrix also showed a loss of glycosaminoglycans. The cellular architecture of the basicranial synchondroses was disorganized, and the nasocerebrally oriented collagen fibrils formed unevenly distributed aggregates. The craniofacial morphology described here for the Gly85 mice shares features typical for other mouse mutations causing short limbed dwarfism. The observations indicate that defective cartilage production causes disproportionate craniofacial growth. Transgenic mice with specific mutations in cartilage-specific genes should therefore be useful for elucidating the complex mechanisms involved in determining the craniofacial growth.