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

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 Paulis, Paolo Vezzoni, Federica Meli, Fiorenzo Antonio Peverali, Caterina Bendotti, Maria Chiara Trolese, Laura PasettoValentina 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, Maria Caramelli, Cesare Galli, Cristina Casalone, Cristiano Corona

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)263-275
Number of pages13
JournalNeurobiology of Disease
Volume124
DOIs
Publication statusPublished - Apr 1 2019

Keywords

  • ALS
  • Amyotrophic lateral sclerosis
  • SOD1
  • TDP-43
  • Transgenic pig

ASJC Scopus subject areas

  • Neurology

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  • Cite this

    Crociara, P., Chieppa, M. N., Vallino Costassa, E., Berrone, E., Gallo, M., Lo Faro, M., Pintore, M. D., Iulini, B., D'Angelo, A., Perona, G., Botter, A., Formicola, D., Rainoldi, A., Paulis, M., Vezzoni, P., Meli, F., Peverali, F. A., Bendotti, C., Trolese, M. C., ... Corona, C. (2019). Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1-linked familiar ALS. Neurobiology of Disease, 124, 263-275. https://doi.org/10.1016/j.nbd.2018.11.021