Enamel Agenesis and Aberrant Mineralizations Occur in Enamelin Null Mice

Loss of function (mutation) or deficiency of any one of the matrix proteins or proteinases typically present in forming enamel leads to moderate and in some cases very severe levels of amelogenesis imperfecta. While global changes occurring in teeth and bones of knockout mouse models for the organic components of enamel have been reported, little is known about what happens in the mineral phase when amelogenesis goes seriously awry as seems to be the case in null states for nonamelogenins (Ambn, Enam). Objective: To characterize mineral distribution and acquisition rates within the calcified material covering the labial surfaces of incisors in Enam-/- (null) mice compared to Enam+/+ and Enam+/- mice. Methods: Hemi–maxillae and –mandibles were removed from 7 week old mice of each genotype, rapidly frozen, and lyophilized. Contiguous 1-mm-long strips of enamel organ (EO) cells and underlying calcified tissues were removed, individually weighed, then ashed for 18 h at 575°C. The residues were reweighed to determine the amount of mineral present in each strip. Some incisors of each genotype were also examined by SEM. Results: Mineral acquisition rates in lower incisors were different for each genotype averaging at their peaks about 42 µg/mm and 88% mineral by weight (MBW), 13 µg/mm and 82% MBW and 5 µg/mm and 67% MBW for Enam+/+, +/-, and -/- mice respectively. Surprisingly, substantial quantities of mineral were also detected within EO cell strips on incisors of Enam-/- mice accounting for as much as 42% of the total mineral present along the labial surfaces of these teeth. Conclusions: Enamelin directly or indirectly influences the total quantity of mineral that develops in enamel. In the absence of enamelin, EO cells form ectopic calcifications and teeth are covered by a crusty material resembling bone in mineral composition. Supported by NIDCR grant DE 11301.