A Suite of Ameloblast Cre and Fluorescent Alleles for Studying Amelogenesis

Amelogenesis, the formation of dental enamel, is driven by specialized epithelial cells called ameloblasts, which undergo successive stages of differentiation. Developmental defects in enamel are common in humans, and they can greatly impact the well-being of affected individuals. Our understanding of amelogenesis and developmental pathologies is based on epithelial Cre drivers, using promoters such as Krt14, Krt5, or Amelx. Most available mouse models do not allow targeting, visualization, and isolation of different ameloblast subpopulations, making it difficult to dissect mechanisms. Herein, we report on the design and verification of a toolkit of 7 mouse alleles that include ameloblast stage-specific Cre recombinases (Ambn^Cre, Amelx^p2A-Cre, Ambn^CreERT2, Klk4^Cre, and Klk4^CreERT2) and fluorescent reporter alleles (Ambn^p2A-eGFP and Klk4^mCherry). We show that these alleles recombine and report in both mouse adult incisors and developing molars, making them suitable for studying tooth development and regeneration. These alleles will enable the study of a wide range of transcriptional, proteomic, and cell signaling events during amelogenesis at unprecedented resolution.