Abstract
FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam20A-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM20A. By breeding K14-Cre mice with Fam20Aflox/flox mice, we created K14-Cre;Fam20Aflox/flox (conditional knock out, cKO) mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography, histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam20A-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice. The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.
Highlights
At postnatal day 0, FAM20A signals were absent from the ameloblasts but were present in the odontoblasts in the mandibular first molars of Fam20AlacZ-flox/+ mice (Figure 2b); at this time point, FAM20A signals were observed in both the ameloblasts and odontoblasts of the mandibular incisor; in the incisor, FAM20A was localized in the secretory stage ameloblasts (Figure 2b and 2b1)
At postnatal day 11, when the mandibular first molar was in its eruptive phase, a significant level of FAM20A was observed in the reduced enamel epithelium (Figure 2f, arrows)
A previous study showed the expression of FAM20A in ameloblasts and odontoblasts,[21] there has been a lack of systematic profiling for the expression of FAM20A in dental tissues
Summary
The FAM20 family (family with sequence similarity 20) consists of the three following members: FAM20A, FAM20B and FAM20C.1 Recent findings have led to great excitement about this small family of proteins, which have endoplasmic reticulum-entry signal sequences responsible for directing proteins into the secretory pathway and which appear to be involved in the post-translational modifications of secretory proteins.FAM20C is a kinase that phosphorylates many extracellular matrix proteins involved in biomineralization and other biological processes.[2,3] FAM20C is ubiquitously expressed,[1,4,5] and mutations in the human FAM20C gene cause Raine syndrome, an autosomal recessive disorder that demonstrates a broad spectrum of clinical manifestations.[6,7,8,9,10] Fam20C-deficient mice developed hypophosphataemic rickets, along with severe dental defects.[11,12]FAM20B is a kinase that catalyses the attachment of phosphate to xylose, which is a step essential to the assembly of glycosaminoglycans during the synthesis of proteoglycans.[13]. FAM20C is a kinase that phosphorylates many extracellular matrix proteins involved in biomineralization and other biological processes.[2,3] FAM20C is ubiquitously expressed,[1,4,5] and mutations in the human FAM20C gene cause Raine syndrome, an autosomal recessive disorder that demonstrates a broad spectrum of clinical manifestations.[6,7,8,9,10] Fam20C-deficient mice developed hypophosphataemic rickets, along with severe dental defects.[11,12]. Constitutive inactivation of Fam20B in mice was embryonically lethal,[14] whereas conditional deletion of Fam20B in the rodent dental epithelium led to supernumerary incisors.[15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
