| 1596 Rescue of Tooth Eruption and Dental Phenotype Characterization of Transgenic Op/Op Mice Expressing Membrane Bound CSF-1 | ||
|
J. DICKSON, K. WOODRUFF, J. SCHULZE, M. MACDOUGALL, and S.L. ABBOUD, University of Texas Health Science Center at San Antonio, USA Two isoforms of macrophage colony-stimulating factor (CSF)-1, soluble (s) and membrane-bound (m), are synthesized by osteoblasts and odontoblasts. In the op/op mouse, absence of osteoblast-derived CSF-1 leads to decreased osteoclasts , osteopetrosis, and failure of tooth eruption. To determine if mCSF-1 can reverse the defect, transgenic mice harboring the human mCSF-1 cDNA under the control of the osteocalcin (OC) promoter were generated and crossbred with heterozygous op/wt mice to establish op/op mutants expressing the transgene (op/opT). Objective: To characterize the dental phenotype of the op/opT mice. Methods: The op/op genotype and transgene expression were confirmed by PCR and Southern blot analysis, respectively. Mandibules of op/opT mice were dissected and either prepared for histology or used to isolate incisors for RT-PCR analysis of tooth matrix gene expression. Total mRNA was isolated using RNA STAT-60 (TEL-TEST, Inc.), converted to cDNA with random primers, and used for PCR amplification of tooth transcripts. Results: High levels of mCSF-1 protein were detected in bone extracts but not in other non-dental tissues or plasma. Op/opT mice showed delayed tooth eruption (15 versus 10 days) with gross morphological and structural abnormalities. Incisors were translucent white, susceptible to breakage, malaligned, and constricted at the incisal tip. Semi-quantitative RT-PCR analysis normalized to GAPDH levels, showed a significant increase in Amg, Ambn, EMSP-1,Dmp1 and DSPP transcripts in teeth of op/opT mice versus controls. Increases ranged from 0.75 fold for Amg to 3.0 fold for DSPP. Conclusions: Expression of mCSF in the op/op background results in abnormal tooth formation and matrix mineralization mimicking amelogenesis imperfecta. These studies demonstrate for the first time that mCSF regulates tooth matrix gene expression. Additional studies are necessary to determine if the effects of mCSF are specific to amelogenesis, dentinogenesis, or a general phenomenon. Supported by grants VA Merit Award (SLA), AR42306 (SLA), & DE09875 (MM). | ||
| Seq #201 - Senior Category 11:00 AM-12:15 PM, Saturday, 15 March 2003 Henry B. Gonzalez Convention Center Exhibit Hall C | ||
|
Back to the AADR/Warner Lambert Hatton Competition Program
| ||