{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:29:02Z","timestamp":1788568142790,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"Paradifference Foundation and ZonMwVeni","doi-asserted-by":"publisher","award":["09150162010197"],"award-info":[{"award-number":["09150162010197"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms25137262","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterisation of an Adult Zebrafish Model for SDHB-Associated Phaeochromocytomas and Paragangliomas"],"prefix":"10.3390","volume":"25","author":[{"given":"Jasmijn B.","family":"Miltenburg","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6525AG Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marnix","family":"Gorissen","sequence":"additional","affiliation":[{"name":"Department of Plant and Animal Biology, Radboud Institute for Biological and Environmental Sciences, Radboud University, 6525AJ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7657-7397","authenticated-orcid":false,"given":"Inge","family":"van Outersterp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6525AG Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Versteeg","sequence":"additional","affiliation":[{"name":"Department of Plant and Animal Biology, Radboud Institute for Biological and Environmental Sciences, Radboud University, 6525AJ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Plant and Animal Biology, Radboud Institute for Biological and Environmental Sciences, Radboud University, 6525AJ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5227-3527","authenticated-orcid":false,"given":"Richard J.","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Genetics, Radboud Center for Mitochondrial Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, 6525AG Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5417-8272","authenticated-orcid":false,"given":"Antonius E.","family":"van Herwaarden","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Radboud University Medical Center, 6525AG Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre J.","family":"Olthaar","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Radboud University Medical Center, 6525AG Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benno","family":"Kusters","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud University Medical Center, 6525AG Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catleen","family":"Conrad","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri J. L. M.","family":"Timmers","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6525AG Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margo","family":"Dona","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6525AG Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1097\/01.hjh.0000251887.01885.54","article-title":"Pheochromocytoma: Presentation, diagnosis and treatment","volume":"24","author":"Reisch","year":"2006","journal-title":"J. Hypertens."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jhawar, S., Arakawa, Y., Kumar, S., Varghese, D., Kim, Y.S., Roper, N., Elloumi, F., Pommier, Y., Pacak, K., and Del Rivero, J. 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