Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1-linked familiar ALS

Autor: Federica Meli, Paolo Vezzoni, Maria Chiara Trolese, Valentina Bonetto, Caterina Bendotti, Cristina Casalone, Maria Consuelo Valentini, Maria Novella Chieppa, Donato Formicola, Matilde Ghibaudi, Elena Vallino Costassa, Giovanna Lazzari, Marina Boido, Barbara Iulini, Maria Domenica Pintore, Elena Berrone, Monica Lo Faro, Paola Crociara, Laura Pasetto, Fiorenzo Antonio Peverali, Corinne Quadalti, Andrea Perota, Irina Lagutina, Alberto Botter, Cesare Galli, Marianna Paulis, Roberto Duchi, Marina Gallo, Maria Silvia Gennero, Antonio D'Angelo, Giovanni Perona, Maria Caramelli, Daniela Dezzutto, Alberto Rainoldi, Cristiano Corona, Rosanna Desiato
Rok vydání: 2018
Předmět:
Zdroj: Neurobiology of Disease, Vol 124, Iss, Pp 263-275 (2019)
ISSN: 1095-953X
Popis: 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.
Databáze: OpenAIRE