ArticleBiochemical and biophysical research communications2019
Muscle fiber-type selective propensity to pathology in the nmd mouse model of SMARD1.
Article in Biochemical and biophysical research communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 7 citations in OpenAlex.
- Klotho Deficiency Promotes Skeletal Muscle Weakness and Is Associated with Impaired Motor Unit Connectivity.International journal of molecular sciences · 2025Article
- Klotho deficiency promotes skeletal muscle weakness and is associated with impaired motor unit connectivity.bioRxiv : the preprint server for biology · 2025Article
- Ighmbp2 mutations and disease pathology: Defining differences that differentiate SMARD1 and CMT2S.Experimental neurology · 2025Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an autosomal recessive disease that causes distal limb muscle atrophy, due to motor neuron degeneration. Similar to other motor neuron diseases, SMARD1 shows differential vulnerability to denervation in various muscle groups, which is recapitulated in the nmd mouse, a model of SMARD1. In multiple neurodegenerative disease models, transcriptomic analysis has identified differentially expressed genes between vulnerable motor neuron populations, but the mechanism leading to susceptibility is largely unknown. To investigate if denervation vulnerability is linked to intrinsic muscle properties, we analyzed muscle fiber-type composition in muscles from motor units that show different degrees of denervation in nmd mice: gastrocnemius, tibialis anterior (TA), and extensor digitorum longus (EDL). Our results revealed that denervation vulnerability correlated with atrophy and loss of MyHC-IIb and MyHC-IIx muscle fiber types. Interestingly, increased vulnerability also correlated with an increased abundance of MyHC-I and MyHC-IIa muscle fibers. These results indicated that MyHC-IIx muscle fibers are the most vulnerable to denervation, followed by MyHC-IIb muscle fibers. Moreover, our data indicate that type MyHC-IIa and MyHC-IIb muscle fibers show resistance to denervation and compensate for the loss of MyHC-IIx and MyHC-IIb muscle fibers in the most vulnerable muscles. Taken together these results provide a basis for the selective vulnerability to denervation of specific muscles in nmd mice and identifies new targets for potential therapeutic intervention.
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