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Minimal Amelogenin Domain for Enamel Formation

Geng, Shuhui and Lei, Yaping and Snead, Malcolm L. (2021) Minimal Amelogenin Domain for Enamel Formation. JOM - Journal of the Minerals, Metals and Materials Society, 73 (6). pp. 1696-1704. ISSN 1047-4838. PMCID PMC8386916. doi:10.1007/s11837-021-04687-x. https://resolver.caltech.edu/CaltechAUTHORS:20210514-134934098

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Abstract

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 in vitro data showing that a 42-amino acid amelogenin-derived peptide (ADP7) mimicked the 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. In vivo, ADP7 peptide partially replaced the function of the full-length amelogenin protein and its several protein isoforms. Protein structure–function relationships identified through in vitro assays can be deployed in whole model animals using CRISPR-Cas9 to validate the function of a minimal protein domain to be translated for clinical use as an enamel biomimetic.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1007/s11837-021-04687-xDOIArticle
https://rdcu.be/ckDNYPublisherFree ReadCube access
ORCID:
AuthorORCID
Snead, Malcolm L.0000-0002-4496-6478
Additional Information:© 2021 The Minerals, Metals & Materials Society. Received 30 December 2020; Accepted 31 March 2021; Published 07 May 2021. Discussions with colleagues were instructive and appreciated. The comments of the three anonymous reviewers served to improve the manuscript and we are grateful for their guidance. The authors declare that they have no conflicts of interest.
Funders:
Funding AgencyGrant Number
NIHR37 DE13045
Issue or Number:6
PubMed Central ID:PMC8386916
DOI:10.1007/s11837-021-04687-x
Record Number:CaltechAUTHORS:20210514-134934098
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210514-134934098
Official Citation:Geng, S., Lei, Y. & Snead, M.L. Minimal Amelogenin Domain for Enamel Formation. JOM 73, 1696–1704 (2021). https://doi.org/10.1007/s11837-021-04687-x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109135
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:14 May 2021 20:57
Last Modified:30 Aug 2021 17:21

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