Coordinated differentiation of the ameloblast cell layer is essential to enamel matrix
protein deposition and subsequent mineralization. It has been hypothesized that this process is governed by Cx43-based gap junctional intercellular communication as
oculodentodigital dysplasia (
ODDD) patients harboring autosomal-dominant mutations in
Cx43 exhibit enamel defects typically resulting in early adulthood
tooth loss. To assess the role of
Cx43 in tooth development we employ a mouse model of
ODDD that harbors a G60S
Cx43 mutant, Gja1(Jrt)/+, and appears to exhibit
tooth abnormalities that mimic the human disease. We found that total
Cx43 plaques at all stages of ameloblast differentiation, as well as within the supporting cell layers, were greatly reduced in Gja1(Jrt)/+ incisors compared to wild-type littermate controls. To characterize the Gja1(Jrt)/+ mouse tooth phenotype, mice were sacrificed prior to tooth eruption (postnatal day 7), weaning (postnatal day 21), and adulthood (2 months postnatal). A severely disorganized Gja1(Jrt)/+ mouse ameloblast layer and abnormal accumulation of
amelogenin were observed at stages when the cells were active in secretion and mineralization. Differences in enamel thickness became more apparent after tooth eruption and incisor exposure to the oral cavity suggesting that enamel integrity is compromised, leading to rapid erosion. Additional analysis of incisors from mutant mice revealed that they were longer with a thicker dentin layer than their wild-type littermates, which may reflect a mechanical stress response to the depleted enamel layer. Together, these data show that reduced levels of
Cx43 gap junctions result in ameloblast dysregulation,
enamel hypoplasia, and secondary tissue responses.