Abstract
Mutations in the gene encoding family with sequence similarity 20, member A (FAM20A) caused amelogenesis imperfecta (AI), in humans. However, the roles of FAM20A in amelogenesis and dentinogenesis are poorly understood. In this study, we generated a Fam20a knockout (Sox2-Cre;Fam20afl/fl) mouse model by crossing Fam20afl/fl mice with Sox2-Cre transgenic mice, in which Fam20a was ablated in both dental epithelium and dental mesenchyme. We found that these mice developed an enamel phenotype that resembles human AI associated with FAM20A mutations, but did not have apparent dentin defects. The secretory stage ameloblasts in the mandibular incisors from the Sox2-Cre;Fam20afl/fl mice were shorter and detached from the enamel matrix, and subsequently lost their polarity, became disorganized and formed numerous spherical extracellular matrices in place of normal enamel. At the molecular level, the Sox2-Cre;Fam20afl/fl mice displayed dramatically reduced expression levels of the genes encoding the enamel matrix proteins, but unaltered levels of the genes encoding the dentin matrix proteins. Moreover, Fam20a ablation resulted in a great decrease in FAM20C protein level, but it did not alter the intracellular localization of FAM20C protein in ameloblasts and odontoblasts. These results indicate that FAM20A is essential for amelogenesis, but is dispensable for dentinogenesis.
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Acknowledgements
This work was supported by National Institute of Dental and Craniofacial Research [Grant Numbers DE022549 (to CQ), DE027345 (to YL and CQ)].
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LL and SF contributed to design, data acquisition, analysis and interpretation, drafted and critically revised the manuscript. HZ and SW contributed to data acquisition, analysis, drafted and critically revised the manuscript; QX contributed to data acquisition, analysis and critically revised the manuscript; CQ contributed to conception, interpretation, drafted and critically revised the manuscript; YL contributed to conception, design, interpretation, drafted and critically revised the manuscript. All authors approved the final version of the submitted manuscript and agreed to be accountable for all aspects of the work.
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Li, L., Saiyin, W., Zhang, H. et al. FAM20A is essential for amelogenesis, but is dispensable for dentinogenesis. J Mol Hist 50, 581–591 (2019). https://doi.org/10.1007/s10735-019-09851-x
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DOI: https://doi.org/10.1007/s10735-019-09851-x