Enamel defects in Acp4R110C/R110C mice and human ACP4 mutations
| dc.contributor.author | Liang, Tian | |
| dc.contributor.author | Wang, Shih-Kai | |
| dc.contributor.author | Smith, Charles | |
| dc.contributor.author | Zhang, Hong | |
| dc.contributor.author | Hu, Yuanyuan | |
| dc.contributor.author | Seymen, Figen | |
| dc.contributor.author | Koruyucu, Mine | |
| dc.contributor.author | Kasımoğlu, Yelda | |
| dc.contributor.author | Kim, Jung-wook | |
| dc.contributor.author | Zhang, Chuhua | |
| dc.contributor.author | Saunders, Thomas L. | |
| dc.contributor.author | Simmer, James P. | |
| dc.contributor.author | Hu, Jan C-C. | |
| dc.date.accessioned | 2022-10-03T07:23:28Z | |
| dc.date.available | 2022-10-03T07:23:28Z | |
| dc.date.issued | 2022 | en_US |
| dc.department | Fakülteler, Diş Hekimliği Fakültesi, Çocuk Diş Hekimliği Ana Bilim Dalı | en_US |
| dc.description.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. | en_US |
| dc.identifier.citation | Liang, T., Wang, S. K., Smith, C., Zhang, H., Hu, Y., Seymen, F., Koruyucu, M., Kasımoğlu, Y., Kasımoğlu, Y., Kim, J.-W., Zhang, C., Saunders, T. L., Simmer, J. P., Hu, J. C-C. (2022). Enamel defects in Acp4R110C/R110C mice and human ACP4 mutations. Scientific Reports, 12(1). | en_US |
| dc.identifier.issue | 1 | en_US |
| dc.identifier.scopus | 2-s2.0-85139158485 | |
| dc.identifier.scopusquality | Q1 | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12939/2973 | |
| dc.identifier.volume | 12 | en_US |
| dc.identifier.wos | WOS:000862559400028 | |
| dc.identifier.wosquality | Q1 | |
| dc.indekslendigikaynak | Web of Science | |
| dc.indekslendigikaynak | Scopus | |
| dc.indekslendigikaynak | PubMed | |
| dc.institutionauthor | Seymen, Figen | |
| dc.language.iso | en | |
| dc.relation.ispartof | Scientific Reports | |
| dc.relation.isversionof | 10.1038/s41598-022-20684-9 | en_US |
| dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
| dc.rights | info:eu-repo/semantics/openAccess | en_US |
| dc.subject | ACP4 | en_US |
| dc.title | Enamel defects in Acp4R110C/R110C mice and human ACP4 mutations | |
| dc.type | Article |
