ABNORMAL ENAMEL DEVELOPMENT IN A CYSTIC-FIBROSIS TRANSGENIC MOUSE MODEL

Cystic fibrosis (CF) is a hereditary condition that affects cAMP-regul ated chloride channels in epithelial tissues due to a defect in the cy stic fibrosis transmembrane conductance regulator (CFTR) gene. Recentl y, a transgenic CF mouse model was developed at UNC that exhibits no C FTR expression. Interestingly, the CF mouse demonstrates abnormal inci sor enamel. Therefore, the purpose of this investigation was to charac terize the enamel in this CF mouse model. Incisors from CF and normal mice were evaluated by light microscopy (LM), scanning electron micros copy (SEM), and transmission electron microscopy (TEM). The enamel pro teins were examined by amino acid analysis, SDS-PAGE, and Western blot . Gross examination showed that 100% of CF mice had soft, chalky white incisor enamel, while the enamel of normal mice was hard and yellow-b rown. LM indicated that the ameloblasts in the CF mice underwent prema ture degeneration shortly after completion of the secretory phase. The CF mouse enamel appeared to be of relatively normal thickness and sho wed a prism structure similar to that of normal mouse enamel. However, the CF mouse enamel crystallites appeared to have a rough granular su rface compared with normal enamel. SDS-PAGE indicated that mature CF e namel retained low-molecular-weight material (approximate to 20 kDa), whereas normal mature enamel did not. This low-molecular-weight materi al cross-reacted with anti-amelogenin antibodies in Western blot analy sis. This investigation shows that abnormal CFTR expression in the mou se results in developmental abnormalities in the incisor enamel. Altho ugh further investigation is required to determine the mechanism leadi ng to abnormal enamel formation, the CF mouse provides a potentially u seful animal model for investigating aberrant enamel development.