ArticleHuman molecular genetics2017
Amelogenesis imperfecta caused by N-terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- A splicing-derived microRNA from amelogenin exon4 regulates enamel formation via control of exon4 splicing and amelogenin expression.Scientific reports · 2026Article
- Challenges of Studying Amelogenesis in Gene-Targeted Mouse Models.International journal of molecular sciences · 2025Review
- Article
- HeterozygousJournal of medical genetics · 2024Article
- Novel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes.Journal of dental research · 2024Article
- The Dynamic Interactions of a Multitargeting Domain in Ameloblastin Protein with Amelogenin and Membrane.International journal of molecular sciences · 2023Article
- Enamel Structure Defects inBiomedicines · 2023Article
- Article
- Identification of stages of amelogenesis in the continuously growing mandiblular incisor of C57BL/6J male mice throughout life using molar teeth as landmarks.Frontiers in physiology · 2023Article
- The phosphorylation of serineMatrix biology : journal of the International Society for Matrix Biology · 2022Article
- Loss of BMP2 and BMP4 Signaling in the Dental Epithelium Causes Defective Enamel Maturation and Aberrant Development of Ameloblasts.International journal of molecular sciences · 2022Article
- Enamel Defects Associated With Dentin Sialophosphoprotein Mutation in Mice.Frontiers in physiology · 2021Article
- Altered CaBiochimica et biophysica acta. Molecular cell research · 2018Review
- Amelogenesis Imperfecta; Genes, Proteins, and Pathways.Frontiers in physiology · 2017Review
- The Unfolded Protein Response in Amelogenesis and Enamel Pathologies.Frontiers in physiology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
'Amelogenesis imperfecta' (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans. Our data indicate that the mutation inhibits the ameloblast secretory pathway leading to ER stress and an activated unfolded protein response (UPR). Initially, with the support of the UPR acting in pro-survival mode, Enamp.S55I heterozygous mice secreted structurally normal enamel. However, enamel secreted thereafter was structurally abnormal; presumably due to the UPR modulating ameloblast behaviour and function in an attempt to relieve ER stress. Homozygous mutant mice failed to produce enamel. We also identified a novel heterozygous ENAMp.L31R mutation causing AI in humans. We hypothesize that ER stress is the aetiological factor in this case of human AI as it shared the characteristic phenotype described above for the Enamp.S55I mouse. We previously demonstrated that AI in mice carrying the Amelxp.Y64H mutation is a proteinopathy. The current data indicate that AI in Enamp.S55I mice is also a proteinopathy, and based on comparative phenotypic analysis, we suggest that human AI resulting from the ENAMp.L31R mutation is another proteinopathic disease. Identifying a common aetiology for AI resulting from mutations in two different genes opens the way for developing pharmaceutical interventions designed to relieve ER stress or modulate the UPR during enamel development to ameliorate the clinical phenotype.
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