Influence of genetic background on fluoride metabolism in mice

The A/J and 129P3/J inbred mouse strains have been reported to have different susceptibilities to dental fluorosis (DF) which has been attributed to their genetic backgrounds. Objective: This study was done to determine whether susceptibility to DF could be explained by differences in fluoride (F) metabolism. Methods: Weanling, male A/J mice (susceptible to DF, n=18) and 129P3/J mice (resistant, n=18) were housed in pairs and assigned to three groups given low-F food (0.95 ppm) and water containing 0, 10 or 50 ppm F. Because preliminary results indicated that the A/J mice drank nearly twice as much water, their water F concentration [F] was adjusted weekly to approximate F intake by the 129P3/J mice for the next seven weeks. Weekly F intake, excretion and retention and terminal plasma and femur F levels were determined. The degree of DF was assessed using clinical criteria and quantitative fluorescence (QF). Data were tested for significant differences using 2-way ANOVA (p<0.05). Results: Compared to the 129P3/J mice given 50 ppm F, significantly higher QF scores (greater degree of DF; 45.6 vs 15.7, p<0.001) were recorded for the A/J mice in the highest water [F] group but not in the intermediate water [F] groups or control groups. Although total F intake did not differ significantly, total F excretion by the A/J mice was significantly higher due to greater urinary F excretion. Thus the 129P3/J mice retained significantly more of their ingested F which was reflected in their higher femur F levels. Although higher in the 129P3/J groups, plasma F levels were not significantly different. Conclusion: It was concluded that (1) these strains differ quantitatively with respect to several features of F metabolism and (2) amelogenesis in the

129P3/J strain is remarkably unaffected by high F exposures. Supported by FAPESP (2005/04671-0), CNPq (471485/2007-1) and NIH/NIDCR (DE014853).