biostudies-literatureGeng SNIDCR NIH HHSNational Institute of Dental and Craniofacial Research1696-1704https://www.ebi.ac.uk/biostudies/studies/S-EPMC8386916biostudies-literatureUnknown73(6)Amelogenin is the most abundant matrix protein guiding hydroxyapatite formation in enamel, the durable bioceramic tissue that covers vertebrate teeth. Here, we sought to refine structure-function for an amelogenin domain based on <i>in vitro</i> data showing a 42 amino acid amelogenin-derived peptide (ADP7) mimicked formation of hydroxyapatite similar to that observed for the full-length mouse 180 amino acid protein. In mice, we used CRISPR-Cas9 to express only ADP7 by the native amelogenin promoter. Analysis revealed ADP7 messenger RNA expression in developing mouse teeth with the formation of a thin layer of enamel. <i>In vivo</i>, ADP7 peptide partially replaced the function of the full-length amelogenin protein and its several protein isoforms. Protein structure-function relationships JOM (Warrendale, Pa. : 1989)Minimal amelogenin domain for enamel formation.PMC8386916R37 DE013045R37 DE13045Geng SLei YSnead MLfalseMinimal amelogenin domain for enamel formation.Amelogenin is the most abundant matrix protein guiding hydroxyapatite formation in enamel, the durable bioceramic tissue that covers vertebrate teeth. Here, we sought to refine structure-function for an amelogenin domain based on <i>in vitro</i> data showing a 42 amino acid amelogenin-derived peptide (ADP7) mimicked formation of hydroxyapatite similar to that observed for the full-length mouse 180 amino acid protein. In mice, we used CRISPR-Cas9 to express only ADP7 by the native amelogenin promoter. Analysis revealed ADP7 messenger RNA expression in developing mouse teeth with the formation of a thin layer of enamel. <i>In vivo</i>, ADP7 peptide partially replaced the function of the full-length amelogenin protein and its several protein isoforms. Protein structure-function relationships 2021-01-01T00:00:00Z2021 Jun2025-04-04T20:15:42.639Z2025-04-04T20:15:42.639ZS-EPMC83869163445653710.1007/s11837-021-04687-x