The distribution and characterization of skeletal muscle lesions in dysferlin-deficient SJL and A/J mice.
The pathogenesis of limb-girdle muscular dystrophy type 2B (LGMD2B) dysferlinopathy remains to be investigated. The distribution and characterization of skeletal muscle lesions were examined in two different LGMD2B mouse models, SJL and A/J mice (at 10 and 35 weeks old), in association with the endoplasmic reticulum (ER) stress. SJL mice showed an earlier age of onset and a faster progression of skeletal muscle lesions as compared with those of A/J mice; the sensitivity difference to muscular dystrophic lesions between SJL and A/J mice was observed in the lumbar muscles (particularly, lumbar longissimus and sublumbar muscles); the lesions seen mainly in SJL mice at 35 weeks old consisted of degeneration, necrosis, fatty infiltration, variation in muscle fiber size and atrophy in muscle fibers. Enzyme-histochemically, the fast-twitch muscle fiber was predominant for the degenerative changes seen in the rectus femoris and lateral longissimus muscles of SJL mice. Immunohistochemically, the main reactive cell type observed in and around degenerative and/or necrotic muscle fibers was macrophages, demonstrable with an anti-F4/80 antibody. Because the analyses of spliced XBP1 mRNA, a marker of ER stress, did not show the increased expression, it was considered that ER stress did not affect the progression of skeletal muscle lesions in SJL mice with the advanced stage of dysferlinopathy.
Kobayashi
Kinji
K
Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka 598-8531, Japan. kobayashi.kinji@me.mt-pharma.co.jp
Izawa
Takeshi
T
Kuwamura
Mitsuru
M
Yamate
Jyoji
J
D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004195:Disease Models, Animal; D000073939:Dysferlin; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; C497505:Dysf protein, mouse; D000073939:Dysferlin; D008565:Membrane Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse