121169 20240319081015.0 doi 10.1242/dmm.049083 sideral 131814 ART-2022-131814 eng Hernández-Ainsa, Carmen (orcid)0000-0003-3524-5158 Development and characterization of cell models harbouring mtDNA deletions for <i>in vitro</i> study of Pearson syndrome 2022 Access copy available to the general public Unrestricted Pearson syndrome is a rare multisystem disease caused by single large-scale mitochondrial DNA deletions (SLSMDs). The syndrome presents early in infancy and is mainly characterised by refractory sideroblastic anaemia. Prognosis is poor and treatment is supportive, thus the development of new models for the study of Pearson syndrome and new therapy strategies is essential. In this work, we report three different cell models carrying an SLMSD: fibroblasts, transmitochondrial cybrids and induced pluripotent stem cells (iPSCs). All studied models exhibited an aberrant mitochondrial ultrastructure and defective oxidative phosphorylation system function, showing a decrease in different parameters, such as mitochondrial ATP, respiratory complex IV activity and quantity or oxygen consumption. Despite this, iPSCs harbouring ‘common deletion’ were able to differentiate into three germ layers. Additionally, cybrid clones only showed mitochondrial dysfunction when heteroplasmy level reached 70%. Some differences observed among models may depend on their metabolic profile; therefore, we consider that these three models are useful for the in vitro study of Pearson syndrome, as well as for testing new specific therapies. This article has an associated First Person interview with the first author of the paper. info:eu-repo/grantAgreement/ES/DGA/B33-17R info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI17-00021 info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI20-00340 info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI21-00229 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.3 2022 PATHOLOGY 20 / 76 = 0.263 2022 Q2 T1 CELL BIOLOGY 93 / 191 = 0.487 2022 Q2 T2 1.489 2022 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2022 Q1 Neuroscience (miscellaneous) 2022 Q1 Medicine (miscellaneous) 2022 Q1 Immunology and Microbiology (miscellaneous) 2022 Q1 7.5 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion López-Gallardo, Ester Universidad de Zaragoza (orcid)0000-0002-3217-1424 García-Jiménez, María Concepción Universidad de Zaragoza (orcid)0000-0002-5563-3177 Climent-Alcalá, Francisco José Rodríguez-Vigil, Carmen García Fernández de Villalta, Marta Artuch, Rafael Montoya, Julio Universidad de Zaragoza (orcid)0000-0003-1770-6299 Ruiz-Pesini, Eduardo Universidad de Zaragoza (orcid)0000-0002-0269-7337 Emperador, Sonia Universidad de Zaragoza (orcid)0000-0001-5964-6138 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 1011 670 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Pediatría 15, 3 (2022), [13 pp.] Disease Models & Mechanisms Disease Models & Mechanisms 1754-8403 7290759 http://zaguan.unizar.es/record/121169/files/texto_completo.pdf Versión publicada 3658628 http://zaguan.unizar.es/record/121169/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:121169 articulos driver 2024-03-18-15:34:38 ARTICLE