{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:03:55Z","timestamp":1792047835844,"version":"4.4.0"},"reference-count":31,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":1556,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["PI11\/00678"],"award-info":[{"award-number":["PI11\/00678"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["242193"],"award-info":[{"award-number":["242193"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 la Marat\u00f3 de TV3","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008062","name":"Fundaci\u00f3n Alicia Koplowitz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Frataxin (FXN) deficiency causes Friedreich\u2019s ataxia (FRDA), a multisystem disorder with neurological and non-neurological symptoms. FRDA pathophysiology combines developmental and degenerative processes of dorsal root ganglia (DRG), sensory nerves, dorsal columns and other central nervous structures. A dying-back mechanism has been proposed to explain the peripheral neuropathy and neuropathology. In addition, affected individuals have non-neuronal symptoms such as diabetes mellitus or glucose intolerance. To go further in the understanding of the pathogenic mechanisms of neuropathy and diabetes associated with the disease, we have investigated the humanized mouse YG8R model of FRDA. By biochemical and histopathological studies, we observed abnormal changes involving muscle spindles, dorsal root axons and DRG neurons, but normal findings in the posterior columns and brain, which agree with the existence of a dying-back process similar to that described in individuals with FRDA. In YG8R mice, we observed a large number of degenerated axons surrounded by a sheath exhibiting enlarged adaxonal compartments or by a thin disrupted myelin sheath. Thus, both axonal damage and defects in Schwann cells might underlie the nerve pathology. In the pancreas, we found a high proportion of senescent islets of Langerhans in YG8R mice, which decreases the \u03b2-cell number and islet mass to pathological levels, being unable to maintain normoglycemia. As a whole, these results confirm that the lack of FXN induces different pathogenic mechanisms in the nervous system and pancreas in the mouse model of FRDA: dying back of the sensory nerves, and pancreatic senescence.<\/jats:p>","DOI":"10.1242\/dmm.024273","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T01:13:14Z","timestamp":1460682794000},"page":"647-657","source":"Crossref","is-referenced-by-count":16,"title":["Two different pathogenic mechanisms, dying-back axonal neuropathy and pancreatic senescence, are present in the YG8R mouse model of Friedreich\u2019s ataxia"],"prefix":"10.1242","volume":"9","author":[{"given":"Bel\u00e9n","family":"Moll\u00e1","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF) 1 Program in Rare and Genetic Diseases and IBV\/CSIC Associated Unit at CIPF , , Valencia 46012 , Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) 2 , Valencia 28029 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima","family":"Riveiro","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF) 1 Program in Rare and Genetic Diseases and IBV\/CSIC Associated Unit at CIPF , , Valencia 46012 , Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) 2 , Valencia 28029 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantxa","family":"Bolinches-Amor\u00f3s","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF) 1 Program in Rare and Genetic Diseases and IBV\/CSIC Associated Unit at CIPF , , Valencia 46012 , Spain"},{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF) 3 Cell Therapy Program , , Valencia 46012 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana C.","family":"Mu\u00f1oz-Lasso","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF) 1 Program in Rare and Genetic Diseases and IBV\/CSIC Associated Unit at CIPF , , Valencia 46012 , Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) 2 , Valencia 28029 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8635-5421","authenticated-orcid":false,"given":"Francesc","family":"Palau","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF) 1 Program in Rare and Genetic Diseases and IBV\/CSIC Associated Unit at CIPF , , Valencia 46012 , Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) 2 , Valencia 28029 , Spain"},{"name":"Institut de Recerca Pedi\u00e0trica Hospital San Joan de D\u00e9u 4 Department of Genetic and Molecular Medicine , , Barcelona 08950 , Spain"},{"name":"University of Barcelona School of Medicine 5 Department of Pediatrics , , Barcelona 08036 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Gonz\u00e1lez-Cabo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF) 1 Program in Rare and Genetic Diseases and IBV\/CSIC Associated Unit at CIPF , , Valencia 46012 , Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) 2 , Valencia 28029 , Spain"},{"name":"University of Valencia 6 Department of Physiology, Faculty of Medicine and Dentistry , , Valencia 46010 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061302542522200_DMM024273C1","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1016\/j.ygeno.2006.06.015","article-title":"GAA repeat expansion mutation mouse models of Friedreich ataxia exhibit oxidative stress leading to progressive neuronal and cardiac pathology","volume":"88","author":"Al-Mahdawi","year":"2006","journal-title":"Genomics"},{"key":"2024061302542522200_DMM024273C2","doi-asserted-by":"publisher","first-page":"e107416","DOI":"10.1371\/journal.pone.0107416","article-title":"Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich ataxia","volume":"9","author":"Anjomani Virmouni","year":"2014","journal-title":"PLoS ONE"},{"key":"2024061302542522200_DMM024273C3","doi-asserted-by":"publisher","first-page":"17528","DOI":"10.1073\/pnas.0905523106","article-title":"SH3TC2\/KIAA1985 protein is required for proper myelination and the integrity of the node of Ranvier in the peripheral nervous system","volume":"106","author":"Arnaud","year":"2009","journal-title":"Proc. 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