Phenotypes Associated with This Genotype

Genotype
MGI:2661118

• Allelic Composition: Dysf^tm1Kcam/Dysf^tm1Kcam
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

Muscle inflammation in Dysf^tm1Kcam/Dysf^tm1Kcam mice

cellular

skeletal muscle necrosis ( J:171870 )

skeletal muscle fiber necrosis ( J:83126 )

• significant skeletal muscle necrosis with macrophage infiltration and fat replacement is evident by 8 months of age

immune system

myositis ( J:171870 )

• muscle from 8 month, but not 4 month old, mice shows small numbers of infiltrating lymphocytes; both perivascular and endomysial leukocytes are seen

muscle

skeletal muscle necrosis ( J:171870 )

skeletal muscle fiber necrosis ( J:83126 )

• significant skeletal muscle necrosis with macrophage infiltration and fat replacement is evident by 8 months of age

myositis ( J:171870 )

• muscle from 8 month, but not 4 month old, mice shows small numbers of infiltrating lymphocytes; both perivascular and endomysial leukocytes are seen

abnormal sarcolemma morphology ( J:83126 )

• 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

increased variability of skeletal muscle fiber size ( J:83126 , J:171870 )

• at 9 months of age, a significantly greater muscle fiber size variation is noted in mutant skeletal muscle than in wild-type muscle (J:83126)

centrally nucleated skeletal muscle fibers ( J:83126 , J:171870 )

• ~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 (J:83126)

skeletal muscle fiber degeneration ( J:83126 )

• 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

skeletal muscle fibrosis ( J:171870 )

dystrophic muscle ( J:83126 )

• 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

impaired skeletal muscle regeneration ( J:83126 )

• 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

• mutant skeletal muscle fibres are defective in Ca²⁺-dependent sarcolemma resealing, indicating a disruption of the muscle membrane repair machinery

homeostasis/metabolism

increased circulating creatine kinase level ( J:83126 , J:171870 )

• homozygotes exhibit a several-fold increase in serum creatine kinase levels relative to wild-type mice (J:83126)

• both before and after exercise (J:171870)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2B		DOID:0110276	OMIM:253601	J:83126
distal myopathy		DOID:11720	OMIM:PS160500	J:83126