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Genetic ablation of P65 subunit of NF‐κB in mdx mice to improve muscle physiological function
Author(s) -
Yin Xi,
Tang Ying,
Li Jian,
Dzuricky Anna T.,
Pu Chuanqiang,
Fu Freddie,
Wang Bing
Publication year - 2017
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25517
Subject(s) - duchenne muscular dystrophy , mdx mouse , dystrophin , transgene , muscular dystrophy , skeletal muscle , biology , genetic enhancement , endocrinology , medicine , gene , genetics
Duchenne muscular dystrophy (DMD) is a genetic muscle disease characterized by dystrophin deficiency. Beyond gene replacement, the question of whether ablation of the p65 gene of nuclear factor‐kappa B (NF‐κB) in DMD can improve muscle physiology function is unknown. In this study, we investigated muscle physiological improvement in mdx mice (DMD model) with a genetic reduction of NF‐κB. Methods Muscle physiological function and histology were studied in 2‐month‐old mdx /p65 +/− , wild‐type, mdx , and human minidystrophin gene transgenic mdx (TghΔDys/ mdx ) mice. Results Improved muscle physiological function was found in mdx /p65 +/− mice when compared with mdx mice; however, it was similar to TghΔDys/ mdx mice. The results indicate that genetic reduction of p65 levels diminished chronic inflammation in dystrophic muscle, thus leading to amelioration of muscle pathology and improved muscle physiological function. Conclusions The results show that inhibition of NF‐κB may be a promising therapy when combined with gene therapy for DMD. Muscle Nerve 56 : 759–767, 2017