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Characterisation of an Adult Zebrafish Model for -Associated Phaeochromocytomas and Paragangliomas. | LitMetric

AI Article Synopsis

  • Phaeochromocytomas and paragangliomas (PPGLs) are rare tumors from chromaffin cells, with genetic variants linked to aggressive disease and limited treatment options when they spread.
  • A new research study used adult zebrafish with genetic mutations similar to those in humans to model these PPGLs, aiming to better understand the diseases.
  • Although these zebrafish did not develop visible tumors, they showed significantly higher levels of succinate, a key indicator associated with PPGLs, suggesting the model could help research the disease mechanisms and eventually develop effective therapies.

Article Abstract

Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours arising from chromaffin cells. Pathogenic variants in the gene are associated with malignancy and poor prognosis. When metastases arise, limited treatment options are available. The pathomechanism of -associated PPGL remains largely unknown, and the lack of suitable models hinders therapy development. Germline heterozygous pathogenic variants predispose to developing PPGLs with a life-long penetrance of around 50%. To mimic the human disease phenotype, we characterised adult heterozygous mutant zebrafish as a potential model to study -related PPGLs. Adult mutant zebrafish did not develop an obvious tumour phenotype and were anatomically and histologically like their wild-type siblings. However, mutants showed significantly increased succinate levels, a major hallmark of -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 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 -related PPGLs.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11241774PMC
http://dx.doi.org/10.3390/ijms25137262DOI Listing

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