Key result
Genetic elimination of iNOS did not improve specific twitch and tetanic forces or reduce histological signs of muscle damage in the extensor digitorum longus muscle of dystrophin-deficient mdx4cv mice.
Why the study?
Does genetic elimination of iNOS improve specific force of the extensor digitorum longus muscle in dystrophin-deficient mdx4cv mice?
Does genetic elimination of iNOS improve specific force of the extensor digitorum longus muscle in dystrophin-deficient mdx4cv mice?
Genetic ablation of iNOS does not improve muscle force or reduce nitrosative stress in a mouse model of Duchenne muscular dystrophy, suggesting it plays a minor role in DMD-associated force reduction.
iNOS unlikely a major therapeutic target in DMD; leaves open nitrosative stress contributions in other models or muscles.
Nitrosative stress compromises force generation in Duchenne muscular dystrophy (DMD). Both inducible nitric oxide synthase (iNOS) and delocalized neuronal NOS (nNOS) have been implicated. We recently demonstrated that genetic elimination of nNOS significantly enhanced specific muscle forces of the extensor digitorum longus (EDL) muscle of dystrophin-null mdx4cv mice (Li D et al J. Path. 223:88-98, 2011). To determine the contribution of iNOS, we generated iNOS deficient mdx4cv mice. Genetic elimination of iNOS did not alter muscle histopathology. Further, the EDL muscle of iNOS/dystrophin DKO mice yielded specific twitch and tetanic forces similar to those of mdx4cv mice. Additional studies suggest iNOS ablation did not augment nNOS expression neither did it result in appreciable change of nitrosative stress markers in muscle. Our results suggest that iNOS may play a minor role in mediating nitrosative stress-associated force reduction in DMD.
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Li et al. (2011) studied Duchenne muscular dystrophy (animal model) (n=31). Genetic elimination of iNOS vs. mdx4cv mice (dystrophin-deficient) was evaluated on Specific twitch and tetanic forces of the extensor digitorum longus (EDL) muscle. Genetic elimination of iNOS did not improve specific twitch and tetanic forces or reduce histological signs of muscle damage in the extensor digitorum longus muscle of dystrophin-deficient mdx4cv mice.
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