ArticleHuman molecular genetics2010
A mutation in the mouse Amelx tri-tyrosyl domain results in impaired secretion of amelogenin and phenocopies human X-linked amelogenesis imperfecta.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- [Frameshift mutation inBeijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Article
- Splicing mutations in AMELX and ENAM cause amelogenesis imperfecta.BMC oral health · 2023Article
- 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
- The effects of 4-Phenylbutyric acid on ER stress during mouse tooth development.Frontiers in physiology · 2022Article
- MMP20-generated amelogenin cleavage products prevent formation of fan-shaped enamel malformations.Scientific reports · 2021Article
- Dental Epithelial Stem Cells as a Source for Mammary Gland Regeneration and Milk Producing Cells In Vivo.Cells · 2019Article
- Altered CaBiochimica et biophysica acta. Molecular cell research · 2018Review
- Ablation of Runx2 in Ameloblasts Suppresses Enamel Maturation in Tooth Development.Scientific reports · 2018Article
- Amelogenesis imperfecta caused by N-terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress.Human molecular genetics · 2017Article
- The Unfolded Protein Response in Amelogenesis and Enamel Pathologies.Frontiers in physiology · 2017Review
- Amelogenesis Imperfecta; Genes, Proteins, and Pathways.Frontiers in physiology · 2017Review
- Preparative SDS PAGE as an Alternative to His-Tag Purification of Recombinant Amelogenin.Frontiers in physiology · 2017Article
- Article
- Modeling craniofacial and skeletal congenital birth defects to advance therapies.Human molecular genetics · 2016Review
- Ameloblastin peptide encoded by exon 5 interacts with amelogenin N-terminus.Biochemistry and biophysics reports · 2016Article
- Retinoic Acid Excess Impairs Amelogenesis Inducing Enamel Defects.Frontiers in physiology · 2016Article
- Improved protocol to purify untagged amelogenin - Application to murine amelogenin containing the equivalent P70→T point mutation observed in human amelogenesis imperfecta.Protein expression and purification · 2015Article
- WDR72 models of structure and function: a stage-specific regulator of enamel mineralization.Matrix biology : journal of the International Society for Matrix Biology · 2014Article
- Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate.Human molecular genetics · 2014Article
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10 authors at 4 institutions in 1 country.
Funding
Abstract
Amelogenesis imperfecta (AI) describes a broad group of clinically and genetically heterogeneous inherited defects of dental enamel bio-mineralization. Despite identification of a number of genetic mutations underlying AI, the precise causal mechanisms have yet to be determined. Using a multi-disciplinary approach, we describe here a mis-sense mutation in the mouse Amelx gene resulting in a Y --> H substitution in the tri-tyrosyl domain of the enamel extracellular matrix protein amelogenin. The enamel in affected animals phenocopies human X-linked AI where similar mutations have been reported. Animals affected by the mutation have severe defects of enamel bio-mineralization associated with absence of full-length amelogenin protein in the developing enamel matrix, loss of ameloblast phenotype, increased ameloblast apoptosis and formation of multi-cellular masses. We present evidence to demonstrate that affected ameloblasts express but fail to secrete full-length amelogenin leading to engorgement of the endoplasmic reticulum/Golgi apparatus. Immunohistochemical analysis revealed accumulations of both amelogenin and ameloblastin in affected cells. Co-transfection of Ambn and mutant Amelx in a eukaryotic cell line also revealed intracellular abnormalities and increased cytotoxicity compared with cells singly transfected with wild-type Amelx, mutant Amelx or Ambn or co-transfected with both wild-type Amelx and Ambn. We hypothesize that intracellular protein-protein interactions mediated via the amelogenin tri-tyrosyl motif are a key mechanistic factor underpinning the molecular pathogenesis in this example of AI. This study therefore successfully links phenotype with underlying genetic lesion in a relevant murine model for human AI.
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