C-src deficiency affects tooth development in a site-specific manner

C-src deficiency is characterized by osteopetrosis and failure of tooth eruption due to insufficient bone resorption. But most attention has been paid on odontomatous lesions of incisors in these animals and not much on molars. Through preliminary X-ray surveillance, we frequently encountered fully erupted molars unlike in other osteopetrotic animals. Objectives: To understand general and tooth type-specific effects of c-src deficiency on the development of teeth and periodontal tissues. Methods: C-src(-/-) mice were kept under soft gel-type diet throughout life, fixed by perfusion at post natal day 0 up to 21 months. After soft X-ray analysis, the upper and lower jaws were processed for light and electron microscopy for structural and histochemical analyses. Age-matched wild type and/or heterozygous animals grown under regular diet were similarly processed and examined accordingly. Results: In c-src(-/-) mice, mandibular 1st molar grew well and, in most cases, erupted into oral cavity concomitant with progressive development of periodontal tissues. Severity of tooth impaction increased posteriory in the mandible, and anteriory in the maxilla. In early development, tooth germs except the lower 1st molar occasionally showed signs of punctuate oppression by bone spicules, but unlike in PTHrP null mice, without appreciable disturbances in crown formation. In all teeth examined, predentin layer was much wider in c-src deficient mice than in the wild type animals. Root development was retarded also in all molars, most conspicuously in the upper 1st and 2nd molars. These teeth failed to erupt even with a wide-open eruption pathway. Discussion: and Conclusion: Since osteoblasts are known to be upregulated in c-src(-/-) animals, absence of tooth destruction by bone spicules suggest significant contribution of hypofunctional osteoclasts in the remodeling of alveolar bone. Our data further indicate that c-src deficiency exerts direct effects on dentin mineralization in general, and root development in a site-specific manner.