TY - JOUR
T1 - Haploinsufficiency of utrophin gene worsens skeletal muscle inflammation and fibrosis in mdx mice
AU - Zhou, Lan
AU - Rafael-Fortney, Jill A.
AU - Huang, Ping
AU - Zhao, Xinyu S.
AU - Cheng, Georgiana
AU - Zhou, Xiaohua
AU - Kaminski, Henry J.
AU - Liu, Liping
AU - Ransohoff, Richard M.
PY - 2008/1/15
Y1 - 2008/1/15
N2 - 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.
AB - 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.
KW - Duchenne muscular dystrophy
KW - Fibrosis
KW - Inflammation
KW - Mdx
KW - Mdx/utrn+/-
KW - Mouse model
UR - http://www.scopus.com/inward/record.url?scp=36549027365&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36549027365&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2007.08.029
DO - 10.1016/j.jns.2007.08.029
M3 - Article
C2 - 17889902
AN - SCOPUS:36549027365
SN - 0022-510X
VL - 264
SP - 106
EP - 111
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1-2
ER -