CINECA IRIS Institutional Research Information System
IRIS è il sistema di gestione integrata dei dati della ricerca (persone, progetti, pubblicazioni, attività) adottato dall'Università degli Studi di Torino.
AperTO è l'archivio istituzionale Open Access destinato a raccogliere, rendere visibile e conservare la produzione scientifica dell'Università degli Studi di Torino.
EnglishAmyotrophic Lateral Sclerosis (ALS) is a neural disorder gradually leading to paralysis of the whole body. Alterations in superoxide dismutase SOD1 gene have been linked with several variants of familial ALS. Here, we investigated a transgenic (Tg) cloned swine model expressing the human pathological hSOD1G93A allele. As in patients, these Tg pigs transmitted the disease to the progeny with an autosomal dominant trait and showed ALS onset from about 27 months of age. Post mortem analysis revealed motor neuron (MN) degeneration, gliosis and hSOD1 protein aggregates in brainstem and spinal cord. Severe skeletal muscle pathology including necrosis and inflammation was observed at the end stage, as well. Remarkably, as in human patients, these Tg pigs showed a quite long presymptomatic phase in which gradually increasing amounts of TDP-43 were detected in peripheral blood mononuclear cells. Thus, this transgenic swine model opens the unique opportunity to investigate ALS biomarkers even before disease onset other than testing novel drugs and possible medical devices.
| Titolo: | Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1-linked familiar ALS. | |
| Autori Riconosciuti: | ||
| Autori: | Paola Crociara, Maria Novella Chieppa, Elena Vallino Costassa, Elena Berrone, Marina Gallo, Monica Lo Faro, Maria Domenica Pintore, Barbara Iulini, Antonio D'Angelo, Giovanni Perona, Alberto Botter, Donato Formicola, Alberto Rainoldi, Marianna Paulise, Paolo Vezzoni, Federica Meli, Fiorenzo Antonio Peverali, Caterina Bendotti, Maria Chiara Trolese, Laura Pasetto, Valentina Bonetto, Giovanna Lazzari, Roberto Duchi, Andrea Perota, Irina Lagutina, Corinne Quadalti, Maria Silvia Gennero, Daniela Dezzutto, Rosanna Desiato, Marina Boido, Matilde Ghibaudi, Maria Consuelo Valentini, MariaCaramelli, CesareGalli, Cristina Casalone, Cristiano Corona | |
| Data di pubblicazione: | 2019 | |
| Abstract: | Amyotrophic Lateral Sclerosis (ALS) is a neural disorder gradually leading to paralysis of the whole body. Alterations in superoxide dismutase SOD1 gene have been linked with several variants of familial ALS. Here, we investigated a transgenic (Tg) cloned swine model expressing the human pathological hSOD1G93A allele. As in patients, these Tg pigs transmitted the disease to the progeny with an autosomal dominant trait and showed ALS onset from about 27 months of age. Post mortem analysis revealed motor neuron (MN) degeneration, gliosis and hSOD1 protein aggregates in brainstem and spinal cord. Severe skeletal muscle pathology including necrosis and inflammation was observed at the end stage, as well. Remarkably, as in human patients, these Tg pigs showed a quite long presymptomatic phase in which gradually increasing amounts of TDP-43 were detected in peripheral blood mononuclear cells. Thus, this transgenic swine model opens the unique opportunity to investigate ALS biomarkers even before disease onset other than testing novel drugs and possible medical devices. | |
| Volume: | 124 | |
| Pagina iniziale: | 263 | |
| Pagina finale: | 275 | |
| Digital Object Identifier (DOI): | 10.1016/j.nbd.2018.11.021 | |
| Parole Chiave: | SOD1, Transgenic pig, Amyotrophic lateral sclerosis, ALS, TDP-43 | |
| Rivista: | NEUROBIOLOGY OF DISEASE | |
| Appare nelle tipologie: | 03A-Articolo su Rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| 1-s2.0-S0969996118307526-main.pdf | SOD1-linked familiar ALS | PDF EDITORIALE | Open Access Visualizza/Apri |
Copyright © 2022