PUBLICATION
foxe1 mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations
- Authors
- Raterman, S.T., Wagener, F.A.D.T.G., Zethof, J., Cuijpers, V., Klaren, P.H.M., Metz, J.R., Von den Hoff, J.W.
- ID
- ZDB-PUB-241003-13
- Date
- 2024
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists : (Journal)
- Registered Authors
- Klaren, Peter, Metz, Juriaan R.
- Keywords
- Bamforth‐Lazarus syndrome, FOXE1, craniofacial malformations, gene‐ethanol interactions, hypothyroidism, non‐syndromic cleft palate, zebrafish
- MeSH Terms
-
- Ethanol*/adverse effects
- Phenotype*
- Craniofacial Abnormalities*/chemically induced
- Craniofacial Abnormalities*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Forkhead Transcription Factors*/genetics
- Forkhead Transcription Factors*/metabolism
- Zebrafish*
- Animals
- Mutation*
- SOX9 Transcription Factor/genetics
- SOX9 Transcription Factor/metabolism
- PubMed
- 39360443 Full text @ Dev. Dyn.
Citation
Raterman, S.T., Wagener, F.A.D.T.G., Zethof, J., Cuijpers, V., Klaren, P.H.M., Metz, J.R., Von den Hoff, J.W. (2024) foxe1 mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations. Developmental Dynamics : an official publication of the American Association of Anatomists. :.
Abstract
Background FOXE1 mutations in humans are associated with cleft palate and hypothyroidism. We previously developed a foxe1 mutant zebrafish demonstrating mineralization defects in larvae. In the present study, we investigate the thyroid status and skeletal phenotype of adult foxe1 mutants.
Results Mutant fish have increased expression of tshβ in the pituitary, and of hepatic dio1 and dio2. In plasma, we found higher Mg levels. Together these findings are indicative of hypothyroidism. We further observed mineralization defects in scales due to enhanced osteoclast activity as measured by increased expression levels of tracp, ctsk, and rankl. Gene-environment interactions in the etiology of FOXE1-related craniofacial abnormalities remain elusive, which prompts the need for models to investigate genotype-phenotype associations. We here investigated whether ethanol exposure increases the risk of developing craniofacial malformations in foxe1 mutant larvae that we compared to wild types. We found in ethanol-exposed mutants an increased incidence of developmental malformations and marked changes in gene expression patterns of cartilage markers (sox9a), apoptotic markers (casp3b), retinoic acid metabolism (cyp26c1), and tissue hypoxia markers (hifaa, hifab).
Conclusion Taken together, this study shows that the foxe1 mutant zebrafish recapitulates phenotypes associated with FOXE1 mutations in human patients and a clear foxe1-ethanol interaction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping