Phenotypes Associated with This Genotype

Genotype
MGI:2176866

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

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

Sgca^tm1Kcam/Sgca^tm1Kcam mice display a progressive muscular dystrophy

muscle

muscle phenotype ( J:177563 )

N • mice exhibit normal diaphragm morphology

cardiac muscle necrosis ( J:177563 )

• at 2 months of age

• severe at 1 year of age

cardiomyopathy ( J:177563 )

• at 2 months of age with large areas of necrotic areas, inflammatory infiltration, and centralized nuclei

increased extensor digitorum longus weight ( J:49992 )

• EDL muscle weight is 40% greater than controls

increased soleus weight ( J:49992 )

• soleus muscle weight is 62% greater than in controls

abnormal muscle fiber morphology ( J:49992 )

• earliest pathological changes in skeletal muscles are widely scattered clusters of necrotic myocytes or regenerating myocytes with internally placed nuclei; such clusters increased in number and size as mice age

• fiber splitting is observed in some mutant muscle

abnormal sarcolemma morphology ( J:49992 )

• membrane damage is exhibited in muscles as shown by uptake of Evans blue dye in 4-20 week-old mice, and by elevated serum levels of creatine kinase and muscle-specific pyruvate kinase activity in 7-10 week-old animals

abnormal skeletal muscle fiber morphology ( J:133929 )

centrally nucleated skeletal muscle fibers ( J:49992 )

• at 8 days of age, between 1 and 2.5% of sural triceps and diaphragm myocytes respectively have central nuclei; by 8-16 weeks, more than 70% (as high as 99%) of myocytes have central nuclei

calcified muscle ( J:49992 )

• dystrophic calcification is noted in some muscles in association with myocyte necrosis in mice 8 weeks or older

dystrophic muscle ( J:49992 )

• other dystrophic changes including atrophy, hypertrophy, and endomysial fibrosis are observed in mutant muscle; fatty infiltration is present in some muscles of 16 week old animals

abnormal muscle contractility ( J:49992 )

• the specific P_o of the EDL muscle is 31% lower than that of controls, while in soleus muscle, the P_o is 39% greater

• resistance to passive muscle stretch is 75% greater than in controls

homeostasis/metabolism

increased circulating creatine kinase level ( J:49992 , J:130252 )

• elevated serum levels of creatine kinase activity in 7-10 week-old animals (J:49992)

• mutants show significantly elevated levels of creatine kinase in the blood, relative to wild-type (J:130252)

abnormal circulating pyruvate kinase level ( J:49992 )

• elevated muscle-specific pyruvate kinase activity in serum of 7-10 week-old animals

cardiovascular system

cardiac muscle necrosis ( J:177563 )

• at 2 months of age

• severe at 1 year of age

cardiac fibrosis ( J:177563 )

• mild at 6 months of age

cardiomyopathy ( J:177563 )

• at 2 months of age with large areas of necrotic areas, inflammatory infiltration, and centralized nuclei

heart inflammation ( J:177563 )

immune system

heart inflammation ( J:177563 )

limbs/digits/tail

increased extensor digitorum longus weight ( J:49992 )

• EDL muscle weight is 40% greater than controls

increased soleus weight ( J:49992 )

• soleus muscle weight is 62% greater than in controls

cellular

cardiac muscle necrosis ( J:177563 )

• at 2 months of age

• severe at 1 year of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2D		DOID:0110278	OMIM:608099	J:49992