scholarly journals Differential induction of muscle atrophy pathways in two mouse models of spinal muscular atrophy

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Marc-Olivier Deguise ◽  
Justin G. Boyer ◽  
Emily R. McFall ◽  
Armin Yazdani ◽  
Yves De Repentigny ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Mouse Models ◽  
Muscle Atrophy ◽  
Muscular Atrophy ◽  
Differential Induction

scholarly journals Dysregulation of the Tweak/Fn14 pathway in skeletal muscle of spinal muscular atrophy mice

2021 ◽  
Author(s):  
Katharina E Meijboom ◽  
Emily McFall ◽  
Daniel Anthony ◽  
Benjamin Edwards ◽  
Sabrina Kubinski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Spinal Muscular Atrophy ◽  
Mouse Models ◽  
Muscle Atrophy ◽  
Muscular Atrophy ◽  
Critical Role ◽  
Pharmacological Intervention ◽  
Muscle Pathology ◽  
Developing Muscle

Spinal muscular atrophy (SMA) is a childhood neuromuscular disorder caused by depletion of the survival motor neuron (SMN) protein. SMA is characterized by the selective death of spinal cord motor neurons, leading to progressive muscle wasting. Loss of skeletal muscle in SMA is a combination of denervation-induced muscle atrophy and intrinsic muscle pathologies. Elucidation of the pathways involved is essential to identify the key molecules that contribute to and sustain muscle pathology. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/TNF receptor superfamily member fibroblast growth factor inducible 14 (Fn14) pathway has been shown to play a critical role in the regulation of denervation-induced muscle atrophy as well as muscle proliferation, differentiation and metabolism in adults. However, it is not clear whether this pathway would be important in highly dynamic and developing muscle. We thus investigated the potential role of the TWEAK/Fn14 pathway in SMA muscle pathology, using the severe Taiwanese Smn-/-;SMN2 and the less severe Smn2B/- SMA mice, which undergo a progressive neuromuscular decline in the first three post-natal weeks. Here, we report significantly dysregulated expression of the TWEAK/Fn14 pathway during disease progression in skeletal muscle of the two SMA mouse models. In addition, siRNA-mediated Smn knockdown in C2C12 myoblasts suggests a genetic interaction between Smn and the TWEAK/Fn14 pathway. Further analyses of SMA, Tweak-/- and Fn14-/- mice revealed dysregulated myopathy, myogenesis and glucose metabolism pathways as a common skeletal muscle feature, and providing further evidence in support of a relationship between the TWEAK/Fn14 pathway and Smn. Finally, a pharmacological intervention (Fc-TWEAK) to upregulate the activity of the TWEAK/Fn14 pathway improved disease phenotypes in the two SMA mouse models. Our study provides novel mechanistic insights into the molecular players that contribute to muscle pathology in SMA and into the role of the TWEAK/Fn14 pathway in developing muscle.

scholarly journals Temporal and tissue-specific variability of SMN protein levels in mouse models of spinal muscular atrophy

2018 ◽  
Vol 27 (16) ◽  
pp. 2851-2862 ◽  
Author(s):  
Ewout J N Groen ◽  
Elena Perenthaler ◽  
Natalie L Courtney ◽  
Crispin Y Jordan ◽  
Hannah K Shorrock ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Mouse Models ◽  
Muscular Atrophy ◽  
Tissue Specific ◽  
Protein Levels ◽  
Smn Protein

SMN deficiency alters Nrxn2 expression and splicing in zebrafish and mouse models of spinal muscular atrophy

2013 ◽  
Vol 23 (7) ◽  
pp. 1754-1770 ◽  
Author(s):  
Kelvin See ◽  
Preeti Yadav ◽  
Marieke Giegerich ◽  
Pearl S. Cheong ◽  
Martin Graf ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Mouse Models ◽  
Muscular Atrophy

scholarly journals Pharmacokinetics, pharmacodynamics, and efficacy of a small-moleculeSMN2splicing modifier in mouse models of spinal muscular atrophy

2016 ◽  
Vol 25 (10) ◽  
pp. 1885-1899 ◽  
Author(s):  
Xin Zhao ◽  
Zhihua Feng ◽  
Karen K. Y. Ling ◽  
Anna Mollin ◽  
Josephine Sheedy ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Mouse Models ◽  
Muscular Atrophy

scholarly journals SAHA ameliorates the SMA phenotype in two mouse models for spinal muscular atrophy

2010 ◽  
Vol 19 (8) ◽  
pp. 1492-1506 ◽  
Author(s):  
Markus Riessland ◽  
Bastian Ackermann ◽  
Anja Förster ◽  
Miriam Jakubik ◽  
Jan Hauke ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Mouse Models ◽  
Muscular Atrophy

scholarly journals Motor neuron cell-nonautonomous rescue of spinal muscular atrophy phenotypes in mild and severe transgenic mouse models

2015 ◽  
Vol 29 (3) ◽  
pp. 288-297 ◽  
Author(s):  
Yimin Hua ◽  
Ying Hsiu Liu ◽  
Kentaro Sahashi ◽  
Frank Rigo ◽  
C. Frank Bennett ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Transgenic Mouse ◽  
Mouse Models ◽  
Muscular Atrophy ◽  
Transgenic Mouse Models

scholarly journals Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy

2017 ◽  
Vol 27 (3) ◽  
pp. 130-143 ◽  
Author(s):  
Fazel Shabanpoor ◽  
Suzan M Hammond ◽  
Frank Abendroth ◽  
Gareth Hazell ◽  
Matthew J.A. Wood ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Mouse Models ◽  
Muscular Atrophy ◽  
Brain Delivery ◽  
Morpholino Oligonucleotide
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