Phenotypes Associated with This Genotype

Genotype
MGI:3621491

• Allelic Composition: Dmd^mdx/Dmd^mdx
• Genetic Background: C57BL/10ScSn-Dmd^mdx/J

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

muscle

abnormal muscle morphology ( J:7361 )

♀

dilated sarcoplasmic reticulum ( J:7361 )

♀

abnormal skeletal muscle fiber morphology ( J:7361 )

♀ • development of electron-dense bodies in the mitochondria resulting in swelling and degenerating mitochondria, and disruption of the plasmalemma basal lamina

♀ • the normal myofibrillar architecture of bands and lines disappears and myofilaments disintegrate and become misaligned

increased skeletal muscle fiber diameter ( J:226314 )

♀ • tibialis anterior muscle fibers are increased in diameter (1500 m²) as compared to C57BL/10ScSn mice (375-750 m²)

increased variability of skeletal muscle fiber size ( J:7361 )

♀ • variable muscle fiber size; progressive starting at 3 weeks of age

centrally nucleated skeletal muscle fibers ( J:226314 )

♀ • mice exhibit an increased number of centrally nucleated fibers

♀ • Background Sensitivity: increase is less than in Dmd^mdx mice on the DBA/2J background than in mice on the C57BL/10ScSn background

♀ • Background Sensitivity: myonuclei are predominantly centrally located in contrast to juxtasarcolemmal position in mice on the DBA/2J background

increased skeletal muscle mass ( J:226314 )

♀ • increase in muscle mass in gastrocnemius, tibialis anterior and quadriceps as compared to controls

♀ • increased muscle mass in EDL as compared to C57BL/10ScSn control at 28 and 52 weeks of age

♀ • Background Sensitivity: increased muscle mass in EDL as compared to Dmd^mdx mice on the DBA/2J background at 7, 28 and 52 weeks of age

skeletal muscle hypertrophy ( J:226314 )

♀ • muscle hypertrophy observed in gastrocnemius, tibialis anterior and quadriceps

♀ • Background Sensitivity: hypertrophy is not observed in Dmd^mdx mice on the DBA/2J background

skeletal muscle fibrosis ( J:7361 )

♀ • exhibit mild muscle fibrosis, however there is no replacement of lost muscle by fat cells

skeletal muscle necrosis ( J:7361 )

♀ • progressive starting at 9 weeks of age

calcified muscle ( J:226314 )

♀ • calcium deposits are observed in quadriceps at 52 weeks of age

♀ • Background Sensitivity: however, Dmd^mdx mice on the DBA/2J background develop calcium deposits by 7 weeks of age

dystrophic muscle ( J:7361 , J:226314 )

♀ (J:7361)

♀ • onset of muscular dystrophy is earlier and more severe in Dmd^mdx mice on the DBA/2J background (J:226314)

muscle degeneration ( J:7361 )

♀ • progressive starting at 3 weeks of age

skeletal muscle degeneration ( J:226314 )

♀ • lesions that are observed in quadriceps and diaphragm exhibit muscle degeneration, regeneration and mononuclear infiltrating cells at 7 weeks of age

♀ • increased uptake of Evans blue dye, a measure of muscle damage, as compared to C57BL/10ScSn controls at 8 weeks of age

♀ • Background Sensitivity: however, uptake is lower than in Dmd^mdx mice on the DBA/2J background

muscular atrophy ( J:7361 )

♀ • progressive starting at 3 weeks of age

abnormal muscle physiology ( J:3666 )

♀ • increased intracellular sodium concentration in muscle; increased severity with age

decreased cardiac muscle contractility ( J:226314 )

♀ • lower ejection fraction and shortening fraction than C57BL/10ScSn controls at 52 weeks of age

♀ • Background Sensitivity: ejection fraction and shortening fraction are higher than in Dmd^mdx mice on the DBA/2J background at 28 weeks of age

cardiomyopathy ( J:226314 )

♀ • cardiomyopathy is observed at 28 weeks of age

♀ • Background Sensitivity: cardiomyopathy is observed at 7 weeks of age in Dmd^mdx mice on the DBA/2J background

myositis ( J:226314 )

♀ • hindlimb and forelimb inflammation (as measured by cathepsin activity) is observed at 7 weeks of age

♀ • inflammation and mononuclear cell infiltration is observed in the quadriceps beginning at 7 weeks of age

♀ • Background Sensitivity: unlike Dmd^mdx mice on the DBA/2J background inflammation is not observed in the forelimbs at 52 weeks of age

impaired skeletal muscle contractility ( J:226314 )

♀ • decrease in specific force generation in extensor digitorum longus (EDL) as compared to C57BL/10ScSn controls at 28 and 52 weeks of age

♀ • Background Sensitivity: increase in specific and maximum force generation in EDL as compared to Dmd^mdx mice on the DBA/2J background

abnormal skeletal muscle regeneration ( J:226314 )

♀ • lesions that are observed in quadriceps and diaphragm exhibit muscle degeneration, regeneration and mononuclear infiltrating cells at 7 weeks of age

myopathy ( J:7361 )

♀ • progressive degenerative myopathy; increased severity with age

reproductive system

reduced female fertility ( J:7361 )

♀ • slight reduction in fertility

cardiovascular system

cardiovascular system phenotype ( J:226314 )

♀N • Background Sensitivity: mice do not exhibit inflammation in cardiac tissue in contrast to Dmd^mdx mice on the DBA/2J background

enlarged heart ( J:226314 )

♀ • enlarged heart as compared to C57BL/10ScSn controls

♀ • enlargement is significant at 52 weeks of age

decreased cardiac output ( J:226314 )

♀

decreased cardiac stroke volume ( J:226314 )

♀

decreased cardiac muscle contractility ( J:226314 )

♀ • lower ejection fraction and shortening fraction than C57BL/10ScSn controls at 52 weeks of age

♀ • Background Sensitivity: ejection fraction and shortening fraction are higher than in Dmd^mdx mice on the DBA/2J background at 28 weeks of age

cardiomyopathy ( J:226314 )

♀ • cardiomyopathy is observed at 28 weeks of age

♀ • Background Sensitivity: cardiomyopathy is observed at 7 weeks of age in Dmd^mdx mice on the DBA/2J background

growth/size/body

enlarged heart ( J:226314 )

♀ • enlarged heart as compared to C57BL/10ScSn controls

♀ • enlargement is significant at 52 weeks of age

increased body size ( J:226314 )

♀ • mice have increased body mass as compared to C57BL/10ScSn controls

♀ • Background Sensitivity: mice have increased body mass as compared to Dmd^mdx mice on the DBA/2J background at 28 weeks

hearing/vestibular/ear

abnormal auditory brainstem response waveform shape ( J:105938 )

♀ • prolonged brainstem auditory evoked potential peak and interpeak latencies after noise exposure

increased or absent threshold for auditory brainstem response ( J:105938 )

♀ • significantly increased hearing threshold after noise exposure

increased susceptibility to noise-induced hearing loss ( J:105938 )

♀ • daily exposure to noise for 1 month increased hearing threshold and prolonged brainstem auditory evoked potential peak and interpeak latencies

homeostasis/metabolism

increased circulating creatine kinase level ( J:7361 , J:226314 )

♀ • exhibit elevated blood levels of creatine kinase (J:7361)

♀ • elevated levels of serum creatine kinase as compared to C57BL/10ScSn controls at 24 and 28 weeks (J:226314)

♀ • Background Sensitivity: levels are higher than Dmd^mdx mice on the DBA/2J background at 24 weeks (J:226314)

abnormal circulating pyruvate kinase level ( J:7361 )

♀ • exhibit elevated blood levels of pyruvate kinase

increased creatine kinase activity ( J:226314 )

♀ • increased creatine kinase activity as compared to C57BL/10ScSn controls at 24 and 28 weeks

♀ • Background Sensitivity: activity is higher than Dmd^mdx mice on the DBA/2J background at 24 weeks

immune system

increased interferon-gamma secretion ( J:150572 )

♀ • in splenocytes at 2 weeks of age

increased interleukin-12 secretion ( J:150572 )

♀ • in splenocytes at 2 weeks of age

increased interleukin-2 secretion ( J:150572 )

♀ • in splenocytes at 2 weeks and 2 years of age

increased interleukin-4 secretion ( J:150572 )

♀ • in splenocytes at 2 weeks, 4 weeks, and 2 years of age

increased interleukin-6 secretion ( J:150572 )

♀ • in splenocytes at 2 weeks of age

increased tumor necrosis factor secretion ( J:150572 )

♀ • in splenocytes at 2 weeks of age

myositis ( J:226314 )

♀ • hindlimb and forelimb inflammation (as measured by cathepsin activity) is observed at 7 weeks of age

♀ • inflammation and mononuclear cell infiltration is observed in the quadriceps beginning at 7 weeks of age

♀ • Background Sensitivity: unlike Dmd^mdx mice on the DBA/2J background inflammation is not observed in the forelimbs at 52 weeks of age

behavior/neurological

impaired coordination ( J:106640 )

♀ • performance is similar to that observed in double knockouts

abnormal grip strength ( J:106640 )

♀ • performance is similar to that observed in double knockouts

decreased grip strength ( J:226314 )

♀ • reduced forelimb and hindlimb grip strength beginning at 6 weeks as compared to controls

♀ • Background Sensitivity: forelimb grip strength is less than Dmd^mdx mice on the DBA/2J background at 28 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:7361