Mouse Genome Informatics
hm1
    Dysftm1Kcam/Dysftm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• plasma membrane disruptions are identified with Evans blue by 8 months of age
• however, minimal sarcolemma damage is detected in mutant muscle after exercise, indicating the presence of a functional dystrophin-glycoprotein complex (DGC) and stable sarcolemma
• at 9 months of age, a significantly greater muscle fiber size variation is noted in mutant skeletal muscle than in wild-type muscle
• ~10% of all fibers in mutant skeletal muscle are centrally nucleated by 2 months of age, 20% by 4 months of age, and 48% and 65% by 8 and 10 months, respectively
• active skeletal muscle regeneration occurs in response to muscle degeneration, as evidenced by the presence of centrally nucleated skeletal muscle fibers and increased variability in fiber size
• significant skeletal muscle necrosis with macrophage infiltration and fat replacement is evident by 8 months of age
• homozygotes develop a slowly progressive muscular dystrophy at the level of single muscle fibers, as evidenced by the presence of individual Evans-blue positive fibers
• the % of centrally nucleated fibers increases with age, with a few individual necrotic and centrally nucleated fibers first evident at 2 months of age
• by 8 months of age, dystrophic skeletal muscle exhibits regenerating fibers, split fibers, and muscle necrosis with macrophage infiltration, and fat replacement
• the severity of muscle pathology varies in different skeletal muscles
• in response to sarcolemma injuries, mutant skeletal muscle fibers display sub-sarcolemmal vesicle accumulations, whereas wild-type damaged fibers exhibit only dysferlin-enriched membrane patches
• unlike wild-type muscle fibres, mutant skeletal muscle fibres are defective in Ca2+-dependent sarcolemma resealing, indicating a disruption of the muscle membrane repair machinery

homeostasis/metabolism
• homozygotes exhibit a several-fold increase in serum creatine kinase levels relative to wild-type mice


Mouse Genome Informatics
cx2
    C3tm1Crr/C3tm1Crr
Dysftm1Kcam/Dysftm1Kcam

B6.129-Dysftm1Kcam C3tm1Crr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• significantly reduced dystrophic phenotype