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

Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1-linked familiar ALS. Neurobiol Dis. 2018 Nov 21;: Authors: Crociara P, Chieppa MN, Costassa EV, Berrone E, Gallo M, Faro ML, Pintore MD, Iulini B, D'Angelo A, Perona G, Botter A, Formicola D, Rainoldi A, Paulis M, Vezzoni P, Meli F, Peverali FA, Bendotti C, Trolese MC, Pasetto L, Bonetto V, Lazzari G, Duchi R, Perota A, Lagutina I, Quadalti C, Gennero MS, Dezzutto D, Desiato R, Boido M, Ghibaudi M, Valentini MC, Caramelli M, Galli C, Casalone C, Corona C 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 mononucle...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research