Project R-15680

Application of tooth organoids as mirror of rare disorders affecting mineral metabolism (Research)

Amelogenesis imperfecta (AI) is a heterogeneous group of rare inherited disorders affecting development of enamel in both primary and permanent teeth, and may occur as an isolated trait or in association with other symptoms in syndromes (often associated with the kidney, bone, skin and many other organs). Such syndromes often present with severe dental complications similar to skeletal disorders related to the extracellular matrix or to mineral metabolism. Patients with mutations in CLDN16, CLDN10, CNNM2, and GNA11 (OMIM: 248250, 617671, 616418, 145981) have been diagnosed with AI. Understanding how these proteins, and more broadly disruptions in magnesium and calcium metabolism, are involved during amelogenesis, can be achieved through access to patients, affected teeth, and genetic mouse models mirroring these rare disorders. However, an urgent need remains to develop suitable in vitro tools to model these diseases and their molecular underpinnings, including their effects on ameloblasts and enamel. Therefore, in this project, we propose to develop state-of-the-art 3D in vitro organoid models, from diseased mouse models as well as from patient material. Developed organoids will be essential to advance our understanding of these diseases, of their dental phenotype(s), and in guiding treatment development. At the same time, development of such organoid systems enables us to reduce the usage of laboratory animals, in line with European and national 3R principles.

01 January 2025 - 31 December 2026