Preliminary study of the dentition in Stim1/Stim2 deficient mice

Objectives: Calcium release activated calcium (CRAC) channels are important for Ca²⁺ influx in enamel cells. The main molecular components of CRAC channels are the endoplasmic reticulum Ca²⁺ sensor STIM1 and the plasma membrane pore sub-unit ORAI1. Patients with a genetic mutation in ORAI1 and STIM1 genes suffer not only from severe immunodeficiency, but also from a hypomineralized enamel phenotype that is highly reminiscent of amelogenesis imperfecta (AI). However, the role/s of STIM and ORAI in enamel remains limited as global Stim1^-/- and Orai1^-/- mice die perinatally for unknown reasons. To solve this issue we have developed conditional KO mice lacking both STIM1 and STIM2 and examined their dental phenotype.
Methods: The dentition of Stim1^-/-Stim2^-/- mice was assessed by histological procedures as well as by micro-CT, hardness testing, and electron microscopy.
Results: Micro-CT analysis shows severe enamel loss in Stim1^-/-Stim2^-/- mice. The tooth regions that had preserved any enamel show a much stronger radiolucency than controls. Micro hardness testing reveals a significantly softer enamel indicating compromised mechanical properties. Backscattered SEM analysis confirms that the enamel layer in Stim1^-/-Stim2^-/- is hypomineralized. Other lines of evidence suggest that enamel cells in Stim1^-/-Stim2^-/- show up-regulation of Ca²⁺ -induced stress markers and abnormal Ca²⁺ transport system.
Conclusions: These data highlight the importance of Ca²⁺ influx via CRAC channels and the role of STIM proteins in dental enamel mineralization.