Haploinsufficiency of utrophin gene worsens skeletal muscle inflammation and fibrosis in mdx mice

Lan Zhou, Jill A. Rafael-Fortney, Ping Huang, Xinyu S. Zhao, Georgiana Cheng, Xiaohua Zhou, Henry J. Kaminski, Liping Liu, Richard M. Ransohoff

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

To address whether mdx mice with haploinsufficiency of utrophin (mdx/utrn+/-) develop more severe skeletal muscle inflammation and fibrosis than mdx mice, to represent a better model for Duchenne muscular dystrophy (DMD), we performed qualitative and quantitative analysis of skeletal muscle inflammation and fibrosis in mdx and mdx/utrn+/- littermates. Inflammation was significantly worse in mdx/utrn+/- quadriceps at age 3 and 6 months and in mdx/utrn+/- diaphragm at age 3 but not 6 months. Fibrosis was more severe in mdx/utrn+/- diaphragm at 6 months, and at this age, mild fibrosis was noted in quadriceps of mdx/utrn+/- but not mdx mice. The findings indicate that utrophin compensates, although insufficiently, for the effects of dystrophin loss with regard to inflammation and fibrosis of both quadriceps and diaphragm muscles in mdx mice. With more severe muscle dystrophy than mdx mice and a longer life span than utrophin-dystrophin-deficient (dko) mice, mdx/utrn+/- mice provide a better mouse model for testing potential therapies for muscle inflammation and fibrosis associated with DMD.

Original languageEnglish (US)
Pages (from-to)106-111
Number of pages6
JournalJournal of the Neurological Sciences
Volume264
Issue number1-2
DOIs
StatePublished - Jan 15 2008

Fingerprint

Utrophin
Inbred mdx Mouse
Haploinsufficiency
Skeletal Muscle
Fibrosis
Inflammation
Diaphragm
Genes
Dystrophin
Duchenne Muscular Dystrophy
Muscles
Quadriceps Muscle

Keywords

  • Duchenne muscular dystrophy
  • Fibrosis
  • Inflammation
  • Mdx
  • Mdx/utrn+/-
  • Mouse model

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Zhou, L., Rafael-Fortney, J. A., Huang, P., Zhao, X. S., Cheng, G., Zhou, X., ... Ransohoff, R. M. (2008). Haploinsufficiency of utrophin gene worsens skeletal muscle inflammation and fibrosis in mdx mice. Journal of the Neurological Sciences, 264(1-2), 106-111. https://doi.org/10.1016/j.jns.2007.08.029

Haploinsufficiency of utrophin gene worsens skeletal muscle inflammation and fibrosis in mdx mice. / Zhou, Lan; Rafael-Fortney, Jill A.; Huang, Ping; Zhao, Xinyu S.; Cheng, Georgiana; Zhou, Xiaohua; Kaminski, Henry J.; Liu, Liping; Ransohoff, Richard M.

In: Journal of the Neurological Sciences, Vol. 264, No. 1-2, 15.01.2008, p. 106-111.

Research output: Contribution to journalArticle

Zhou, L, Rafael-Fortney, JA, Huang, P, Zhao, XS, Cheng, G, Zhou, X, Kaminski, HJ, Liu, L & Ransohoff, RM 2008, 'Haploinsufficiency of utrophin gene worsens skeletal muscle inflammation and fibrosis in mdx mice', Journal of the Neurological Sciences, vol. 264, no. 1-2, pp. 106-111. https://doi.org/10.1016/j.jns.2007.08.029
Zhou, Lan ; Rafael-Fortney, Jill A. ; Huang, Ping ; Zhao, Xinyu S. ; Cheng, Georgiana ; Zhou, Xiaohua ; Kaminski, Henry J. ; Liu, Liping ; Ransohoff, Richard M. / Haploinsufficiency of utrophin gene worsens skeletal muscle inflammation and fibrosis in mdx mice. In: Journal of the Neurological Sciences. 2008 ; Vol. 264, No. 1-2. pp. 106-111.
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