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 language | English |
|---|---|
| Pages (from-to) | 263-275 |
| Number of pages | 13 |
| Journal | Neurobiology of Disease |
| Volume | 124 |
| DOIs | |
| Publication status | Published - Apr 1 2019 |
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Keywords
- ALS
- Amyotrophic lateral sclerosis
- SOD1
- TDP-43
- Transgenic pig
ASJC Scopus subject areas
- Neurology
Cite this
Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1-linked familiar ALS. / Crociara, Paola; Chieppa, Maria Novella; Vallino Costassa, Elena; Berrone, Elena; Gallo, Marina; Lo Faro, Monica; Pintore, Maria Domenica; Iulini, Barbara; D'Angelo, Antonio; Perona, Giovanni; Botter, Alberto; Formicola, Donato; Rainoldi, Alberto; Paulis, Marianna; Vezzoni, Paolo; Meli, Federica; Peverali, Fiorenzo Antonio; Bendotti, Caterina; Trolese, Maria Chiara; Pasetto, Laura; Bonetto, Valentina; Lazzari, Giovanna; Duchi, Roberto; Perota, Andrea; Lagutina, Irina; Quadalti, Corinne; Gennero, Maria Silvia; Dezzutto, Daniela; Desiato, Rosanna; Boido, Marina; Ghibaudi, Matilde; Valentini, Maria Consuelo; Caramelli, Maria; Galli, Cesare; Casalone, Cristina; Corona, Cristiano.
In: Neurobiology of Disease, Vol. 124, 01.04.2019, p. 263-275.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1-linked familiar ALS
AU - Crociara, Paola
AU - Chieppa, Maria Novella
AU - Vallino Costassa, Elena
AU - Berrone, Elena
AU - Gallo, Marina
AU - Lo Faro, Monica
AU - Pintore, Maria Domenica
AU - Iulini, Barbara
AU - D'Angelo, Antonio
AU - Perona, Giovanni
AU - Botter, Alberto
AU - Formicola, Donato
AU - Rainoldi, Alberto
AU - Paulis, Marianna
AU - Vezzoni, Paolo
AU - Meli, Federica
AU - Peverali, Fiorenzo Antonio
AU - Bendotti, Caterina
AU - Trolese, Maria Chiara
AU - Pasetto, Laura
AU - Bonetto, Valentina
AU - Lazzari, Giovanna
AU - Duchi, Roberto
AU - Perota, Andrea
AU - Lagutina, Irina
AU - Quadalti, Corinne
AU - Gennero, Maria Silvia
AU - Dezzutto, Daniela
AU - Desiato, Rosanna
AU - Boido, Marina
AU - Ghibaudi, Matilde
AU - Valentini, Maria Consuelo
AU - Caramelli, Maria
AU - Galli, Cesare
AU - Casalone, Cristina
AU - Corona, Cristiano
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - ALS
KW - Amyotrophic lateral sclerosis
KW - SOD1
KW - TDP-43
KW - Transgenic pig
UR - http://www.scopus.com/inward/record.url?scp=85057778742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057778742&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2018.11.021
DO - 10.1016/j.nbd.2018.11.021
M3 - Article
AN - SCOPUS:85057778742
VL - 124
SP - 263
EP - 275
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
ER -