Are mouse molars a practicable model for DDE investigations?

Background: The high prevalence of Developmental Defects of Enamel (DDE; typically of concern in ≈10% of juveniles) is problematic for dental health due to associated risk of caries and public concerns about water fluoridation. Prevention should be possible in many cases if aetiology is better understood. Although epidemiology provides useful clues, animal experiments are critical for control over key variables (genetics, nutrition, environment). Mouse molars hold many attractions as a model including experimental flexibility (e.g. toxicology, gene-knockouts), rapid development (3 weeks), similarity to human molars, extensive developmental and genetic characterisation, and accessibility of formative enamel cells for biochemical analyses. However the size of mouse molars (2mm) raises questions about practicability. Recently we adapted several classical analyses to mouse molars (Turnbull et al. JBC (2004) 279:55850-54), but the induction and characterisation of DDE remains to be established. Objectives: (1) To evaluate practicability of undertaking advanced microstructural characterisation of mouse molars. (2) To see whether authentic fluorotic lesions can be induced in mouse molars. Methods: First molars were examined from inbred mice at 2 weeks – 3 months old (both sexes, n = 45). To induce fluorosis, NaF (30-60 mg F/kg) was administered intraperitoneally during the enamel maturation phase (8–10 days old). Microanalyses were done with SEM (structure, chemical resistance), polarised-LM (porosity) and micro-CT (density, morphology). Results: (1) With normal controls, SEM showed prism patterns that varied with chemical treatment, polarised-LM showed enamel birefringence, and micro-CT revealed variable enamel thickness. (2) After fluoride exposure, SEM revealed dose-responsive fluorotic lesions that appeared authentic (surface mottling, subsurface porosity). Conclusions: While technically demanding, it is practicable to induce authentic fluorotic lesions in mouse molars and characterise them quantitatively using a variety of microstructural approaches. Mouse molars therefore constitute a potentially valuable model for investigations of DDE aetiology.