Dental abnormalities associated with failure of tooth eruption in src knockout and op/op mice

c-src knockout and op/op mice develop osteopetrosis as a result of defectiv e osteoclast function and osteoclast formation, respectively. The mutant mi ce can be distinguished readily from their wild-type littermates around 10- 12 days after birth because their incisors do not erupt, but the morphology of their teeth and surrounding bone has not been reported previously in de tail. Histologic examination of jaws of src-mutant mice reveals unerupted, abnormal incisors within their bony crypts. The tooth roots are distorted b y foci of haphazard proliferation of odontogenic epithelium associated with primitive tooth structures that strongly resemble the tumor-like lesions i n humans, known as odontomas. The crowns of the incisors are fused to the a djacent bone, and the developing periodontal ligament is disordered and hyp ocellular. Osteoclasts are present in the bone surrounding the distorted te eth, but as in other bones in these mice they lack ruffled borders and thus do not resorb effectively. Similar odontogenic proliferation is present ar ound unerupted incisors in op/op mice which form very few osteoclasts, but the amount is significantly less than in src mutant mice, Molars fail to er upt in both types of mutant mice, but they are not accompanied by aberrant odontogenic proliferation. These findings and previous reports of similar a bnormalities in jaws from op/op rats suggest that failure of incisor erupti on and associated proliferation of odontogenic epithelium in osteopetrotic rodents are a direct result of defective osteoclastic bone resorption.