Phenotypes Associated with This Genotype

Genotype
MGI:3798607

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

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

muscle

muscle phenotype ( J:177391 )

♂N • limb and diaphragm muscle weights are similar to controls in mice at 1 year of age

abnormal atrium myocardial trabeculae morphology ( J:150127 )

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

abnormal myocardial fiber morphology ( J:150127 )

♂ • cardiac myocyte disorganization

myocardial fiber degeneration ( J:9638 )

♂ • unlike in wild-type mice, cardiac fiber degeneration with phagocytosis is observed

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

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

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

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

♂ • 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

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

abnormal skeletal muscle fiber morphology ( J:152525 )

♂ • at 15 days of age necrotic fibers are found, occassionally in clusters, at 20 days of age necrotic fibers are numerous as are groups of regenerating fibers with internally placed nuclei, necrotic fibers are most numerous between 30 and 60 days of age and gradually dissapear although a few scattered necrotic fibers are present at 120 and 180 days of age, and the regenerating fibers increase in size after 30 days of age and almost all of the fibers have internally placed nuclei by 60 to 120 days of age, but there is almost no fibrous tissue proliferation or adipose tissue replacement

centrally nucleated skeletal muscle fibers ( J:150127 , J:152525 )

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

♂ (J:152525)

skeletal muscle fiber degeneration ( J:9638 )

♂ • mice exhibit skeletal muscle fiber degeneration with phagocytosis unlike in wild-type mice

skeletal muscle fiber necrosis ( J:152525 )

♂

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

skeletal muscle fibrosis ( J:177391 )

♂ • increased collagen deposition in the diaphragm and quadriceps muscles between 12 weeks and 1 year of age

abnormal muscle contractility ( J:152525 )

♂ • scattered hypercontracted fibers are found by electron microscopy at 10 days of age

impaired skeletal muscle contractility ( J:177391 )

♂ • decrease in the tetanic force produced by the diaphragm and extensor digitorum longus muscles compared to wild-type controls

impaired muscle relaxation ( J:9638 )

♂ • electromyograms reveal peudomyotonia unlike in wild-type mice

behavior/neurological

behavior/neurological phenotype ( J:177391 )

♂N • performance in a rotarod assay is not significantly different from controls in mice at 6 - 20 weeks of age

decreased grip strength ( J:177391 )

♂ • in fore and hind paws

abnormal gait ( J:177391 )

♂ • increased hind paw base width

short stride length ( J:177391 )

♂ • at 1 year of age

fatigue ( J:177391 )

♂ • at 6 weeks of age, display a decrease in rearings after exercise compared to wild-type controls

♂ • at 12 weeks of age, display a decrease in ambulation and increase in rest time after exercise compared to wild-type controls

♂ • at 1 year of age, display a decrease in distance traveled after exercise compared to wild-type controls

♂ • interindividual responses to exercise induced fatigue are highly variable

adipose tissue

decreased body fat mass ( J:177391 )

♂ • decrease in the accumulation of abdominal fat compared to wild-type controls

growth/size/body

decreased body fat mass ( J:177391 )

♂ • decrease in the accumulation of abdominal fat compared to wild-type controls

decreased body weight ( J:177391 )

♂ • between 8 and 20 weeks of age compared to wild-type controls

♂ • however, body size as determined by measures of tibia length or body length is similar to wild-type controls

cardiovascular system

abnormal myocardial fiber morphology ( J:150127 )

♂ • cardiac myocyte disorganization

myocardial fiber degeneration ( J:9638 )

♂ • unlike in wild-type mice, cardiac fiber degeneration with phagocytosis is observed

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 )

♂

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Duchenne muscular dystrophy		DOID:11723	OMIM:310200	J:150127 , J:177391