Dental Fluorosis: Variability among Different Inbred Mouse Strains

Abstract

Concurrent with the decline in dental caries has been an increase in the prevalence of dental fluorosis, a side-effect of exposure to greater than optimal levels of fluoride during amelogenesis. The mechanisms that underlie the pathogenesis of dental fluorosis are not known. We hypothesize that genetic determinants influence an individual's susceptibility or resistance to develop dental fluorosis. We tested this hypothesis using a mouse model system (continuous eruption of the incisors) where genotype, age, gender, food, housing, and drinking water fluoride level can be rigorously controlled. Examination of 12 inbred strains of mice showed differences in dental fluorosis susceptibility/resistance. The A/J mouse strain is highly susceptible, with a rapid onset and severe development of dental fluorosis compared with that in the other strains tested, whereas the 129P3/J mouse strain is least affected, with minimal dental fluorosis. These observations support the contribution of a genetic component in the pathogenesis of dental fluorosis.

Fluoride Induces Endoplasmic Reticulum Stress in Ameloblasts Responsible for Dental Enamel Formation

“…The fluoride ions are postulated to adversely affect the precipitation of hydroxyapatite that forms the enamel structure (15). Although this postulate has merit, it does not adequately explain why different inbred strains of mice had different susceptibilities/resistance to enamel fluorosis, whereas the overall levels of fluoride present in their erupted incisors did not differ significantly (16). Additionally, fluoride concentrations in enamel from unerupted human molars did not correlate positively with fluorosis severity, and it was concluded that individual genetic variation likely plays a role in fluorosis susceptibility (17).…”

Relationship between enamel fluorosis severity and fluoride content

“…For instance, one study by Everett et al [16] showed that factors such as genetic history may affect presence of enamel fluorosis in different individuals. In their study, mice were inbred in order to create populations with similar genotypes.…”

Enamel crystals of mice susceptible or resistant to dental fluorosis: an AFM study

“…The reason for the selection of these two strains is based on the fact that the strain A/J is highly susceptible to dental fluorosis, with a rapid and severe development of the disease when the animal is exposed to F, while the strain 129P3/J is less affected, with a low rate of dental fluorosis 8 . In addition, the phenotypic and genetic differences among animals, and their general availability as standard laboratory strains, have also contributed to their selection.…”

“…The observation that certain ethnic groups are more susceptible to this disease 15,25 led some researchers to investigate the genetic susceptibility of different mice strains to dental fluorosis. It was observed that A/J mice are highly susceptible to dental fluorosis, while 129P3/J mice are little affected 8 , despite retaining more F in the body, which leads to higher femur and plasma F concentrations 5 . A recent study compared the profile of protein expression in kidney of A/J and 129P3/J mice.…”