Phenotypes for Dmd MGI:4359195 MGI Mouse

muscle phenotype ( J:160773 )

N	• Background Sensitivity: no muscle fibrosis is observed in contrast to the fibrosis observed Dmd^mdx mice on the DBA/2 background • Background Sensitivity: grip strength scores are similar to wild-type controls in contrast to Dmd^mdx mice on the DBA/2 background

abnormal muscle morphology ( J:7361 )

abnormal atrium myocardial trabeculae morphology ( J:150127 )

• atrial trabecular formation is impaired such that trabeculae at E14.5 are long and hook shaped

myocardial fiber disarray ( J:150127 )

• cardiac myocyte disorganization

myocardium necrosis ( J:152524 )

• 13 of 65 homozygotes display one or two foci of myocardial necrosis between 26 and 303 days of age and the necrotic fibers have sarcoplasmic vacuolation and loss of nuclei

increased quadriceps weight ( J:160773 )

• Background Sensitivity: weight of quadriceps femoris is greater than both wild-type and Dmd^mdx mice on the DBA/2 background

abnormal muscle development ( J:150127 )

• cultured embryonic muscle stem cells from E11.5 to E17.5 exhibit hyperproliferation and apoptosis

• Pax7+ skeletal muscle stem cell population is reduced and disorganized at E17.5

abnormal myotube morphology ( J:150127 )

• myotube alignment is disrupted early in myogenesis

• muscles exhibit a small reduction in myotube number at E13.5-E17.5

• myotubes are hypotrophic in E13.5-E17.5 muscles

• myotube width varies more in E13.5-E17.5 muscles than in wild-type muscle

• misalignment and tangential displacement of myotubes in intercostal muscles at E13.5-E17.5

• myonuclei are more frequently located centrally and slightly further apart in the myotube at E15.5

• only central nuclei (not peripheral) are present in E15.5 muscles

• myotube defects occur earlier in intercostals at E13.5 than proximal limb muscles at E15.5

dilated sarcoplasmic reticulum ( J:7361 )

abnormal skeletal muscle fiber morphology ( J:7361 , J:152524 )

• development of electron-dense bodies in the mitochondria resulting in swelling and degenerating mitochondria, and disruption of the plasmalemma basal lamina (J:7361)

• the normal myofibrillar architecture of bands and lines disappears and myofilaments disintegrate and become misaligned (J:7361)

• myopathic lesions in skeletal muscle are found by 22 days of age and are characterized by widespread loss of sarcoplasmic structure, vacuolation, and eosinophilia (J:152524)

• myotubes indicative of muscle regeneration are found by 22 days of age and by 31 days of age almost all muscles have numerous myotubes (J:152524)

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:150127 , J:152524 )

• only central nuclei (not peripheral) are present in E15.5 muscles (J:150127)

• 25% of fibers have non-peripheral nuclei at 26 days of age and 53% at 100 to 303 days of age (J:152524)

increased skeletal muscle fiber number ( J:160773 )

• Background Sensitivity: total number of myofibers is greater than total number of myofibers found in Dmd^mdx mice on the DBA/2 background

abnormal intercostal muscle morphology ( J:150127 )

• misalignment and tangential displacement of myotubes in intercostal muscles at E13.5-E17.5

• intercostal muscle fibers are distributed more sparsely at E17.5 and fetuses have reduced intercostal muscle fiber densities

• 37.5% depletion of intercostal myotubes by E17.5

increased skeletal muscle mass ( J:160773 )

• Background Sensitivity: in comparison to Dmd^mdx mice on the DBA/2 background

increased skeletal muscle weight ( J:160773 )

• Background Sensitivity: weights of tibialis anterior and gastrocnemius muscles are greater than both wild-type and Dmd^mdx mice on the DBA/2 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

skeletal muscle fiber necrosis ( J:152524 )

dystrophic muscle ( J:7361 )

muscle degeneration ( J:7361 )

• progressive starting at 3 weeks of age

muscular atrophy ( J:7361 )

• progressive starting at 3 weeks of age

myopathy ( J:7361 )

• progressive degenerative myopathy; increased severity with age

reduced female fertility ( J:7361 )

• slight reduction in fertility

adipose tissue phenotype ( J:160773 )

N	• Background Sensitivity: no fat accumulation is observed in contrast to Dmd^mdx mice on the DBA/2 background

decreased aerobic running capacity ( J:160773 )

• Background Sensitivity: mice run shorter distances than wild-type mice, but run farther than Dmd^mdx mice on the DBA/2 backgroun

myocardial fiber disarray ( J:150127 )

• cardiac myocyte disorganization

myocardium necrosis ( J:152524 )

• 13 of 65 homozygotes display one or two foci of myocardial necrosis between 26 and 303 days of age and the necrotic fibers have sarcoplasmic vacuolation and loss of nuclei

abnormal heart atrium morphology ( J:150127 )

• distention or separation of the myocardial and endocardial cell layers of the atria occurs at E17.5

abnormal atrium myocardial trabeculae morphology ( J:150127 )

• atrial trabecular formation is impaired such that trabeculae at E14.5 are long and hook shaped

thick ventricular wall ( J:150127 )

homeostasis/metabolism phenotype ( J:18080 , J:152524 )

N	• serum T4 and thyroid stimulating hormone are normal (J:18080) • serum pyruvate kinase activity is normal (J:152524)

decreased aerobic running capacity ( J:160773 )

• Background Sensitivity: mice run shorter distances than wild-type mice, but run farther than Dmd^mdx mice on the DBA/2 backgroun

increased circulating creatine kinase level ( J:7361 , J:18080 , J:152524 )

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

• serum creatine kinase is elevated at 2 months of age (J:18080)

• serum creatine kinase activity is elevated between 12 and 200 days of age (J:152524)

abnormal circulating pyruvate kinase level ( J:7361 )

• exhibit elevated blood levels of pyruvate kinase

increased growth hormone level ( J:18080 )

• pituitary growth hormone levels is slightly higher than normal in 8 to 10 month old females

abnormal corticotroph morphology ( J:18080 )

• some corticotrophs have enlarged golgi stacks

increased somatotroph cell size ( J:18080 )

• dilation of the rough endoplasmic reticulum, enlarged golgi apparatus, and the presence of many dense secretory granules of homogeneous size are characteristics of the hypertrophic somatotrophs of homozygotes