Enamel defects in Acp4R110C/R110C mice and human ACP4 mutations
Journal
Scientific reports
Journal Volume
12
Journal Issue
1
Date Issued
2022-10-01
Author(s)
Liang, Tian
Smith, Charles
Zhang, Hong
Hu, Yuanyuan
Seymen, Figen
Koruyucu, Mine
Kasimoglu, Yelda
Kim, Jung-Wook
Zhang, Chuhua
Saunders, Thomas L
Simmer, James P
Hu, Jan C-C
Abstract
Human ACP4 (OMIM*606362) encodes a transmembrane protein that belongs to histidine acid phosphatase (ACP) family. Recessive mutations in ACP4 cause non-syndromic hypoplastic amelogenesis imperfecta (AI1J, OMIM#617297). While ACP activity has long been detected in developing teeth, its functions during tooth development and the pathogenesis of ACP4-associated AI remain largely unknown. Here, we characterized 2 AI1J families and identified a novel ACP4 disease-causing mutation: c.774_775del, p.Gly260Aspfs*29. To investigate the role of ACP4 during amelogenesis, we generated and characterized Acp4R110C mice that carry the p.(Arg110Cys) loss-of-function mutation. Mouse Acp4 expression was the strongest at secretory stage ameloblasts, and the protein localized primarily at Tomes' processes. While Acp4 heterozygous (Acp4+/R110C) mice showed no phenotypes, incisors and molars of homozygous (Acp4R110C/R110C) mice exhibited a thin layer of aplastic enamel with numerous ectopic mineralized nodules. Acp4R110C/R110C ameloblasts appeared normal initially but underwent pathology at mid-way of secretory stage. Ultrastructurally, sporadic enamel ribbons grew on mineralized dentin but failed to elongate, and aberrant needle-like crystals formed instead. Globs of organic matrix accumulated by the distal membranes of defective Tomes' processes. These results demonstrated a critical role for ACP4 in appositional growth of dental enamel probably by processing and regulating enamel matrix proteins around mineralization front apparatus.
Subjects
PROSTATIC ACID-PHOSPHATASE; RAT INCISOR AMELOBLASTS; SECRETORY AMELOBLASTS; FINE-STRUCTURE; GOLGI-APPARATUS; AMELOGENESIS; PROTEIN; MATRIX; ULTRASTRUCTURE; BIOSYNTHESIS
SDGs
Publisher
NATURE PORTFOLIO
Type
journal article