{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["5(6)"],"submitter":["Serrano RJ"],"pubmed_abstract":["Variants in <i>UBA5</i> have been reported to cause neurological disease with impaired motor function, developmental delay, intellectual disability and brain pathology as recurrent clinical manifestations. <i>UBA5</i> encodes a ubiquitin-activating-like enzyme that activates ufmylation, a post-translational ubiquitin-like modification pathway, which has been implicated in neurodevelopment and neuronal survival. The reason behind the variation in severity and clinical manifestations in affected individuals and the signal transduction pathways regulated by ufmylation that compromise the nervous system remains unknown. Zebrafish have emerged as a powerful model to study neurodegenerative disease due to its amenability for <i>in vivo</i> analysis of muscle and neuronal tissues, high-throughput examination of motor function and rapid embryonic development allowing an examination of disease progression. Using clustered regularly interspaced short palindromic repeats-associated protein 9 genome editing, we developed and characterized zebrafish mutant models to investigate disease pathophysiology. <i>uba5</i> mutant zebrafish showed a significantly impaired motor function accompanied by delayed growth and reduced lifespan, reproducing key phenotypes observed in affected individuals. Our study demonstrates the suitability of zebrafish to study the pathophysiology of <i>UBA5</i>-related disease and as a powerful tool to identify pathways that could reduce disease progression. Furthermore, <i>uba5</i> mutants exhibited widespread mitochondrial damage in both the nervous system and the skeletal muscle, suggesting that a perturbation of mitochondrial function may contribute to disease pathology."],"journal":["Brain communications"],"pagination":["fcad317"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10691876"],"repository":["biostudies-literature"],"pubmed_title":["Genetic model of UBA5 deficiency highlights the involvement of both peripheral and central nervous systems and identifies widespread mitochondrial abnormalities."],"pmcid":["PMC10691876"],"pubmed_authors":["Bryson-Richardson RJ","Palipana D","Ramm G","Calcinotto V","Sonntag C","Oorschot V","Serrano RJ"],"additional_accession":[]},"is_claimable":false,"name":"Genetic model of UBA5 deficiency highlights the involvement of both peripheral and central nervous systems and identifies widespread mitochondrial abnormalities.","description":"Variants in <i>UBA5</i> have been reported to cause neurological disease with impaired motor function, developmental delay, intellectual disability and brain pathology as recurrent clinical manifestations. <i>UBA5</i> encodes a ubiquitin-activating-like enzyme that activates ufmylation, a post-translational ubiquitin-like modification pathway, which has been implicated in neurodevelopment and neuronal survival. The reason behind the variation in severity and clinical manifestations in affected individuals and the signal transduction pathways regulated by ufmylation that compromise the nervous system remains unknown. Zebrafish have emerged as a powerful model to study neurodegenerative disease due to its amenability for <i>in vivo</i> analysis of muscle and neuronal tissues, high-throughput examination of motor function and rapid embryonic development allowing an examination of disease progression. Using clustered regularly interspaced short palindromic repeats-associated protein 9 genome editing, we developed and characterized zebrafish mutant models to investigate disease pathophysiology. <i>uba5</i> mutant zebrafish showed a significantly impaired motor function accompanied by delayed growth and reduced lifespan, reproducing key phenotypes observed in affected individuals. Our study demonstrates the suitability of zebrafish to study the pathophysiology of <i>UBA5</i>-related disease and as a powerful tool to identify pathways that could reduce disease progression. Furthermore, <i>uba5</i> mutants exhibited widespread mitochondrial damage in both the nervous system and the skeletal muscle, suggesting that a perturbation of mitochondrial function may contribute to disease pathology.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023","modification":"2025-04-05T11:46:11.051Z","creation":"2025-04-05T11:46:11.051Z"},"accession":"S-EPMC10691876","cross_references":{"pubmed":["38046095"],"doi":["10.1093/braincomms/fcad317"]}}