AAV-mediated delivery of mutated myostatin propeptide appears insufficient to ameliorate the muscle phenotype of Acta1(H40Y) mice - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2022

AAV-mediated delivery of mutated myostatin propeptide appears insufficient to ameliorate the muscle phenotype of Acta1(H40Y) mice

Isabelle Lefort
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Nicolas Guerchet
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Ana Buj-Bello

Résumé

Nemaline myopathies (NMs) are a clinically heterogenous group of non-dystrophic congenital muscle diseases caused by mutations in at least 14 genes. NMs are characterised by muscle weakness, hypotonia and respiratory insufficiency, with presence of cytoskeletal protein aggregates (nemaline rods or bodies) in skeletal muscle fibers. ACTA1-related NM accounts for about 50% of severe cases of NMs and to date there no curative treatment. Since myostatin inhibition is known to increase skeletal muscle fiber size in various species and muscle hypotrophy is present in nemaline myopathies, we evaluated the benefit of intramuscular injection of an AAV8 vector expressing a mutated myostatin propeptide (PropD76A) in the Acta1(H40Y) mouse model. A dose of 4,53 x 1012 vg was administrated into the tibialis anterior muscle of mutant and wild-type mice at 4 weeks of age and the effect was analyzed 4 weeks post-injection at the histological and functional level. The contralateral muscle received PBS as control. We found that myostatin PropD76A expression did not significantly increase muscle mass or strength in Acta1(H40Y) mice, suggesting that myostatin inhibition alone may not be sufficient to ameliorate the phenotype of ACTA-related nemaline myopathy.
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Dates et versions

hal-04443105 , version 1 (07-02-2024)

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  • HAL Id : hal-04443105 , version 1

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Janek Hyzewicz, Isabelle Lefort, Nicolas Guerchet, Ana Buj-Bello. AAV-mediated delivery of mutated myostatin propeptide appears insufficient to ameliorate the muscle phenotype of Acta1(H40Y) mice. Myology 2022, Sep 2022, Nice, France. ⟨hal-04443105⟩
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