Deciphering the functions of Stromal Interaction Molecule-1 in amelogenesis using AmelX-iCre mice
Bibliographic record
Abstract
Introduction: The intracellular Ca2+ sensor stromal interaction molecule 1 (STIM1) is thought to play a critical role in enamel development, as its mutations cause Amelogenesis Imperfecta (AI). We recently established an ameloblast-specific (AmelX-iCre) Stim1 conditional deletion mouse model to investigate the role of STIM1 in controlling ameloblast function and differentiation in vivo (Stim1 cKO). Our pilot data (Said et al., J. Dent. Res., 2019, 98, 1002–1010) support our hypothesis for a broad role of Stim1 in amelogenesis. This paper aims to provide an in-depth characterization of the enamel phenotype observed in our Stim1 cKO model. Methods: We crossed AmelX-iCre mice with Stim1-floxed animals to develop ameloblast-specific Stim1 cKO mice. Scanning electron microscopy, energy dispersive spectroscopy, and micro- CT were used to study the enamel phenotype. RNAseq and RT-qPCR were utilized to evaluate changes in the gene expression of several key ameloblast genes. Immunohistochemistry was used to detect the amelogenin, matrix metalloprotease 20 and kallikrein 4 proteins in ameloblasts. Results: Stim1 cKO animals exhibited a hypomineralized AI phenotype, with reduced enamel volume, diminished mineral density, and lower calcium content. The mutant enamel phenotype was more severe in older Stim1 cKO mice compared to younger ones and changes in enamel volume and mineral content were more pronounced in incisors compared to molars. Exploratory RNAseq analysis of incisors’ ameloblasts suggested that ablation of Stim1 altered the expression levels of several genes encoding enamel matrix proteins which were confirmed by subsequent RT-qPCR. On the other hand, RT-qPCR analysis of molars’ ameloblasts showed non-significant differences in the expression levels of enamel matrix genes between control and Stim1-deficient cells. Moreover, gene expression analysis of incisors’ and molars’ ameloblasts showed that Stim1 ablation caused changes in the expression levels of several genes associated with calcium transport and mitochondrial kinetics. Conclusions: Collectively, these findings suggest that the loss of Stim1 in ameloblasts may impact enamel mineralization and ameloblast gene expression.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".