Phenotypes Associated with This Genotype

Genotype
MGI:2450243

• Allelic Composition: Dag1^tm2Kcam/Dag1^tm2Kcam; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

muscle

abnormal skeletal muscle morphology ( J:78838 )

• at ~6 weeks, mutant skeletal muscles show loss of dystrophin, dystrobrevin, and the sarcoglycan-sarcospan complex

• during cycles of degeneration, satellite cells are repetitively activated leading to expression of dystroglycan and other components of the DGC in muscle fibers undergoing regeneration

skeletal muscle necrosis ( J:78838 )

• at ~6 weeks, mutant skeletal muscles, including quadriceps, gastrocnemius, tibialis anterior, biceps, gluteus maximus, and diaphragm, display myonecrosis

increased skeletal muscle fiber size ( J:78838 )

• surprisingly, aging mutants develop marked hypertrophy of skeletal muscle fibers

increased skeletal muscle fiber diameter ( J:78838 )

• a >2-fold increase in fiber diameter of the quadriceps and soleus muscle noted at 18 months

increased variability of skeletal muscle fiber size ( J:78838 )

• at ~6 weeks, mutant mice show variation of skeletal muscle fiber size

centrally nucleated skeletal muscle fibers ( J:78838 )

• up to 95% of skeletal muscle fibers exhibit centrally located nuclei

increased skeletal muscle weight ( J:78838 )

• at 15 months, mutants show a widespread increase in wet muscle weight, esp. in the quadriceps and gastrocnemius muscles, where the weight is doubled

dystrophic muscle ( J:78838 )

• at ~6 weeks, mutants exhibit hallmarks of muscular dystrophy, such as myonecrosis, central nucleation, and variation of fiber size

• however, despite ongoing cycles of muscle degeneration, aging mutants exhibit only a mild dystrophy with signs of efficient muscle regeneration and marked skeletal muscle hypertrophy but no signs of fibrosis or fat replacement

homeostasis/metabolism

increased circulating creatine kinase level ( J:78838 )

• mutant mice exhibit significant elevation of serum creatine kinase levels

growth/size/body

increased body size ( J:78838 )

• at 15 months, mutant mice are significantly larger than control littermates

cellular

skeletal muscle necrosis ( J:78838 )

• at ~6 weeks, mutant skeletal muscles, including quadriceps, gastrocnemius, tibialis anterior, biceps, gluteus maximus, and diaphragm, display myonecrosis