Cystic fibrosis (CF) is a hereditary condition that affects cAMP-regulated chloride channels in epithelial tissues due to a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recently, a transgenic CF mouse model was developed at UNC that exhibits no CFTR expression. Interestingly, the CF mouse demonstrates abnormal incisor enamel. Therefore, the purpose of this investigation was to characterize the enamel in this CF mouse model. Incisors from CF and normal mice were evaluated by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The enamel proteins 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-brown. LM indicated that the ameloblasts in the CF mice underwent premature degeneration shortly after completion of the secretory phase. The CF mouse enamel appeared to be of relatively normal thickness and showed a prism structure similar to that of normal mouse enamel. However, the CF mouse enamel crystallites appeared to have a rough granular surface compared with normal enamel. SDS-PAGE indicated that mature CF enamel retained low-molecular-weight material (approximately 20 kDa), whereas normal mature enamel did not. This low-molecular-weight material cross-reacted with anti-amelogenin antibodies in Western blot analysis. This investigation shows that abnormal CFTR expression in the mouse results in developmental abnormalities in the incisor enamel. Although further investigation is required to determine the mechanism leading to abnormal enamel formation, the CF mouse provides a potentially useful animal model for investigating aberrant enamel development.

Despite extensive investigation, the development mechanism or mechanisms resulting in dental fluorosis are unknown. Several hypotheses suggest abnormal matrix synthesis, secretion, and delayed and/or defective matrix degradation with retention of enamel protein. The purpose of this study was to characterize the protein composition of fluorosed human enamel. Nine permanent moderately fluorosed (developed in a 3.2 ppm H2O area) and ten permanent normal control teeth (from individuals with < 0.2 ppm F in their drinking water) were evaluated. The enamel fluoride concentration, protein content, and amino acid composition were determined for each tooth. The enamel proteins were further characterized by gel electrophoresis and by Western blot analysis by means of polyclonal antibodies raised against recombinant amelogenin protein. Fluorotic enamel had significantly elevated (p = 0.0001) F levels compared with normal enamel (mean [F-] fluorosed = 431 ppm; mean [F-] control = 62 ppm). While there was a significantly greater protein content by weight in fluorosed enamel compared with normal enamel (mean fluorosed = 0.27%; mean control = 0.11%), the amino acid profiles were similar for fluorosed and normal enamel. Gel electrophoresis showed fluorosed enamel to have a greater diversity of primarily low-molecular-weight proteins compared with normal enamel. Western blot analysis did not indicate retention of amelogenin in either fluorosed or normal enamel. This investigation showed that the protein content of fluorosed enamel was greater than that of normal enamel; however, the amino acid compositions were similar for fluorosed and normal enamel. Furthermore, there does not appear to be retention of significant amounts of amelogenin in fully mature, moderately fluorosed human enamel. Although delayed removal of the enamel matrix proteins may play a role in the hypomineralization defects seen in fluorosed enamel, the majority of these proteins are absent in the mature tissue of these moderately fluorosed teeth.

The tricho-dento-osseous (TDO) syndrome demonstrates kinky curly hair, thin-pitted enamel, taurodontism, and thickening of cortical bone. The purpose of this investigation was to characterize the phenotypic variation of TDO in 3, previously unreported, kindreds and to examine possible candidates for the genomic TDO locus. Thirty-three affected and 20 unaffected individuals were recruited for prospective analysis. Participants were evaluated clinically and photographed by one examiner. Blood was drawn for genetic linkage analyses and radiographs were taken to assess dental and skeletal characteristics. All TDO individuals with teeth had generalized thin and/or pitted enamel hypoplasia. Taurodontism was present in all affected individuals, but was variably expressed. Unique kinky/curly hair at birth was reported in 85% of affected individuals. The curly hair phenotype was retained in 46% of affected individuals after infancy. Thick cranial bones, lack of visible pneumatization of the mastoid process, and/or obliteration of the calvarial diploë was seen in 97% of affected persons compared with 30% of the unaffected individuals. The findings suggest that curly hair at birth, enamel hypoplasia, and taurodontism are highly penetrant yet clinically variable components of TDO. The ABO, Kell, and Gc loci previously suggested to be linked to TDO were excluded as candidates in this TDO population. This investigation characterizes the marked variability in the expression of skeletal, hair, and dental manifestations. The broad range of TDO phenotypes seen in these families, including a variety of skeletal changes, does not support subdividing TDO into multiple subtypes based on subtle phenotypic differences.

The ability of ameloblasts and the enamel organ to control the influx of ions into the developing enamel is of considerable interest. The development of transgenic mice lacking a cAMP-regulated chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR), provides a model that may prove valuable for the study of ion regulation in developing teeth. The purpose of this investigation was to characterize the mineral content of normal and CF mice. Five homozygous and five heterozygous adult mice having the CFTR knockout transgene were evaluated. The mice were killed with CO2 and their mandibular incisors removed, embedded in methacrylate, and sectioned, and enamel particles from the incisal region were then dissected for analysis. Each particle was analyzed for its calcium, phosphorus, and magnesium content. The normal mice had a mean mineral content of 80.5%, in contrast to the CF mice, that had markedly hypomineralized enamel (mean = 51.5%). The calcium/phosphorus ratios were similar for both groups of mice and were compatible with the enamel consisting primarily of hydroxyapatite mineral. The enamel magnesium content was significantly elevated in the CF mice (mean = 3560 ppm) compared with the normal mice (mean = 2280 ppm). Normal mouse enamel was highly mineralized, while the CF mouse enamel mineral content was significantly reduced and had an elevated level of magnesium. The altered mineral content of CF mouse enamel indicates that CFTR could play an important role in ion regulation and consequently mineralization of mouse enamel.