https://scholars.lib.ntu.edu.tw/handle/123456789/630765
標題: | Enamel defects in Acp4R110C/R110C mice and human ACP4 mutations | 作者: | Liang, Tian SHIH-KAI WANG 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 |
關鍵字: | PROSTATIC ACID-PHOSPHATASE; RAT INCISOR AMELOBLASTS; SECRETORY AMELOBLASTS; FINE-STRUCTURE; GOLGI-APPARATUS; AMELOGENESIS; PROTEIN; MATRIX; ULTRASTRUCTURE; BIOSYNTHESIS | 公開日期: | 1-十月-2022 | 出版社: | NATURE PORTFOLIO | 卷: | 12 | 期: | 1 | 來源出版物: | Scientific reports | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/630765 | ISSN: | 2045-2322 | DOI: | 10.1038/s41598-022-20684-9 |
顯示於: | 牙醫學系 |
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