Enamel alterations in serotonin 2B receptor knockout mice

Dimitrova-Nakov, Sasha; Marchadier, Arnaud; Collet, Corinne; Baudry, Anne; Vidal, Catherine; Kamoun-Goldrat, Agnès; Kellermann, Odile; Goldberg, Michel

doi:10.1111/j.1600-0722.2011.00908.x

Cited by 9 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, the incisor outer enamel with rods running parallel to the enamel surface might be less susceptible to the altered rod–interrod profile caused by truncated FAM83H and therefore exhibit a minor hypoplastic defect. Interestingly, mice with ablation of serotonin 2B receptor ( Htr2b null mice) have a similar molar phenotype of generally thinner enamel with surface roughness, and the enamel microstructure and rod profiles of Htr2b −/− molars were also abnormal (Dimitrova‐Nakov et al, ; Harichane et al, ). Although the alteration of the rod profiles of molar enamel was not well detailed, primarily due to the high complexity of molar enamel microstructure and a lack of standardized methodology for molar characterization, it was clearly indicated that enamel analysis of mutant genotypes based exclusively on incisor defects can be biased (Goldberg, Kellermann, Dimitrova‐Nakov, Harichane, & Baudry, ).…”

Section: Discussionmentioning

confidence: 99%

The Enamel Phenotype in Homozygous Fam83h Truncation Mice

Wang

Smith

et al. 2019

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background Truncation FAM83H mutations cause human autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), an inherited disorder characterized by severe hardness defects in dental enamel. No enamel defects were observed in Fam83h null mice suggesting that Fam83h truncation mice would better replicate human mutations. Methods We generated and characterized a mouse model (Fam83hTr/Tr) expressing a truncated FAM83H protein (amino acids 1–296), which recapitulated the ADHCAI‐causing human FAM83H p.Tyr297* mutation. Results Day 14 and 7‐week Fam83hTr/Tr molars exhibited rough enamel surfaces and slender cusps resulting from hypoplastic enamel defects. The lateral third of the Fam83hTr/Tr incisor enamel layer was thinner, with surface roughness and altered enamel rod orientation, suggesting disturbed enamel matrix secretion. Regular electron density in mandibular incisor enamel indicated normal enamel maturation. Only mildly increased posteruption attrition of Fam83hTr/Tr molar enamel was observed at 7‐weeks. Histologically, the Fam83hTr/Tr enamel organ, including ameloblasts, and enamel matrices at sequential stages of amelogenesis exhibited comparable morphology without overt abnormalities, except irregular and less evident ameloblast Tomes' processes in specific areas. Conclusions Considering Fam83h−/− mice showed no enamel phenotype, while Fam83hTr/Tr (p.Tyr297*) mice displayed obvious enamel malformations, we conclude that FAM83H truncation mutations causing ADHCAI in humans disturb amelogenesis through a neomorphic mechanism, rather than haploinsufficiency.

show abstract

Section: Discussionmentioning

confidence: 99%

The Enamel Phenotype in Homozygous Fam83h Truncation Mice

Wang

Smith

et al. 2019

Molec Gen & Gen Med

View full text Add to dashboard Cite

show abstract

“…Fixed 3 month-old control and cKO molars were used for SEM analysis. SEM samples were etched with 0.1% nitric acid three times for 10 sec each; rinsed in running tap water, and dried and sputter-coated with gold-palladium for SEM as described in [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

TGF-ß Regulates Enamel Mineralization and Maturation through KLK4 Expression

Cho¹,

Haruyama²,

Hall³

et al. 2013

PLoS ONE

Self Cite

View full text Add to dashboard Cite

Transforming growth factor-ß (TGF-ß) signaling plays an important role in regulating crucial biological processes such as cell proliferation, differentiation, apoptosis, and extracellular matrix remodeling. Many of these processes are also an integral part of amelogenesis. In order to delineate a precise role of TGF-ß signaling during amelogenesis, we developed a transgenic mouse line that harbors bovine amelogenin promoter-driven Cre recombinase, and bred this line with TGF-ß receptor II floxed mice to generate ameloblast-specific TGF-ß receptor II conditional knockout (cKO) mice. Histological analysis of the teeth at postnatal day 7 (P7) showed altered enamel matrix composition in the cKO mice as compared to the floxed mice that had enamel similar to the wild-type mice. The µCT and SEM analyses revealed decreased mineral content in the cKO enamel concomitant with increased attrition and thinner enamel crystallites. Although the mRNA levels remained unaltered, immunostaining revealed increased amelogenin, ameloblastin, and enamelin localization in the cKO enamel at the maturation stage. Interestingly, KLK4 mRNA levels were significantly reduced in the cKO teeth along with a slight increase in MMP-20 levels, suggesting that normal enamel maturation is regulated by TGF-ß signaling through the expression of KLK4. Thus, our study indicates that TGF-ß signaling plays an important role in ameloblast functions and enamel maturation.

show abstract

“…In adult, this receptor controls tissue non-specific alkaline phosphatase (TNAP) activity (Baudry et al, 2010), and thereby bone mineralization (Collet et al, 2008). Inactivation of the 5HT 2B R [5HT 2B R knockout (KO) mice] disturbs enamel formation (Harichane et al, 2011; Dimitrova-Nakov et al, 2014). …”

Section: Differential Structural Enamel Alterations Between Incisors mentioning

confidence: 99%

Comparative studies between mice molars and incisors are required to draw an overview of enamel structural complexity

et al. 2014

Self Cite

View full text Add to dashboard Cite

In the field of dentistry, the murine incisor has long been considered as an outstanding model to study amelogenesis. However, it clearly appears that enamel from wild type mouse incisors and molars presents several structural differences. In incisor, exclusively radial enamel is observed. In molars, enamel displays a high level of complexity since the inner part is lamellar whereas the outer enamel shows radial and tangential structures. Recently, the serotonin 2B receptor (5-HT2BR) was shown to be involved in ameloblast function and enamel mineralization. The incisors from 5HT2BR knockout (KO) mice exhibit mineralization defects mostly in the outer maturation zone and porous matrix network in the inner zone. In the molars, the mutation affects both secretory and maturation stages of amelogenesis since pronounced alterations concern overall enamel structures. Molars from 5HT2BR KO mice display reduction in enamel thickness, alterations of inner enamel architecture including defects in Hunter-Schreger Bands arrangements, and altered maturation of the outer radial enamel. Differences of enamel structure were also observed between incisor and molar from other KO mice depleted for genes encoding enamel extracellular matrix proteins. Thus, upon mutation, enamel analysis based exclusively on incisor defects would be biased. In view of the functional relationship between enamel structure and tooth morphogenesis, identification of molecular actors involved in amelogenesis requires comparative studies between mice molars and incisors.

show abstract

Enamel alterations in serotonin 2B receptor knockout mice

Cited by 9 publications

References 26 publications

The Enamel Phenotype in Homozygous Fam83h Truncation Mice

The Enamel Phenotype in Homozygous Fam83h Truncation Mice

TGF-ß Regulates Enamel Mineralization and Maturation through KLK4 Expression

Comparative studies between mice molars and incisors are required to draw an overview of enamel structural complexity

Contact Info

Product

Resources

About