PUBLICATION
Characterisation of an Adult Zebrafish Model for SDHB-Associated Phaeochromocytomas and Paragangliomas
- Authors
- Miltenburg, J.B., Gorissen, M., van Outersterp, I., Versteeg, I., Nowak, A., Rodenburg, R.J., van Herwaarden, A.E., Olthaar, A.J., Kusters, B., Conrad, C., Timmers, H.J.L.M., Dona, M.
- ID
- ZDB-PUB-240713-23
- Date
- 2024
- Source
- International Journal of Molecular Sciences 25(13): (Journal)
- Registered Authors
- Dona, Margo, Gorissen, Marnix, Timmers, Henri
- Keywords
- paraganglioma, phaeochromocytoma, succinate dehydrogenase subunit B (SDHB), zebrafish
- MeSH Terms
-
- Humans
- Phenotype
- Adrenal Gland Neoplasms*/genetics
- Adrenal Gland Neoplasms*/pathology
- Paraganglioma*/genetics
- PubMed
- 39000369 Full text @ Int. J. Mol. Sci.
Abstract
Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours arising from chromaffin cells. Pathogenic variants in the gene succinate dehydrogenase subunit B (SDHB) are associated with malignancy and poor prognosis. When metastases arise, limited treatment options are available. The pathomechanism of SDHB-associated PPGL remains largely unknown, and the lack of suitable models hinders therapy development. Germline heterozygous SDHB pathogenic variants predispose to developing PPGLs with a life-long penetrance of around 50%. To mimic the human disease phenotype, we characterised adult heterozygous sdhb mutant zebrafish as a potential model to study SDHB-related PPGLs. Adult sdhb mutant zebrafish did not develop an obvious tumour phenotype and were anatomically and histologically like their wild-type siblings. However, sdhb mutants showed significantly increased succinate levels, a major hallmark of SDHB-related PPGLs. While basal activity was increased during day periods in mutants, mitochondrial complex activity and catecholamine metabolite levels were not significantly different. In conclusion, we characterised an adult in vivo zebrafish model, genetically resembling human carriers. Adult heterozygous sdhb mutants mimicked their human counterparts, showing systemic elevation of succinate levels despite the absence of a tumour phenotype. This model forms a promising basis for developing a full tumour phenotype and gaining knowledge of the pathomechanism behind SDHB-related PPGLs.
Genes / Markers
Figure Gallery (4 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping