Phenotypes for Des MGI:5762537 MGI Mouse

decreased cardiac muscle contractility ( J:219616 )

• significantly reduced ejection fraction at 2 years of age

• decreased myocardial contractility (dP/dtmax value) at 1 year of age

cardiomyopathy ( J:219616 )

• pathological alterations consistent with cardiomyopathy

dilated cardiomyopathy ( J:219616 )

• typical signs of dilated cardiomyopathy with significantly lower stroke volumes and ejection fractions in conjunction with increased end-systolic and end-diastolic volumes at 2 years of age

abnormal soleus morphology ( J:219616 )

• massive subsarcolemmal protein aggregate pathology, autophagic vacuoles, Z-band streaming, and lysis of myofibrils in soleus muscle at 6 months of age

abnormal Z line morphology ( J:219616 )

• marked Z-band streaming in soleus muscle at 6 months of age

abnormal skeletal muscle fiber morphology ( J:219616 )

• step-wise fiber stretching analysis revealed that chemically skinned small fiber bundles isolated from 4.5-mo-old soleus muscles show markedly higher biomechanical stiffness, i.e., increased restoration force at identical extensions, than wild-type controls, indicating reduced fiber elasticity

• 4 of 5 fibers display passive-stretch-induced ruptures, unlike wild-type fibers

abnormal skeletal muscle fiber mitochondrial morphology ( J:219616 )

• mitochondrial pathology involving multiple skeletal muscle fibers, with focal changes of cytochrome C oxidase and succinate dehydrogenase enzyme activities in soleus muscle at 3 months of age

• focal accumulation or depletion of mitochondria as well as giant mitochondria in soleus muscle at 16 months of age, as shown by COX staining

increased variability of skeletal muscle fiber size ( J:219616 )

• age-related increase in pathological fiber size variations in soleus muscle

centrally nucleated skeletal muscle fibers ( J:219616 )

• age-related increase in centralized myonuclei in soleus muscle

skeletal muscle degeneration ( J:219616 )

• moderate degenerative changes in soleus muscle at 3 months of age, with signs of myofibril degeneration at 6 months of age

skeletal muscle fiber degeneration ( J:219616 )

• age-related increase in fiber degeneration in soleus muscle, with signs of myofibril lysis at 6 months of age

skeletal muscle endomysial fibrosis ( J:219616 )

• age-related increase in endomysial connective tissue in soleus muscle

dystrophic muscle ( J:219616 )

• age-related progression of dystrophic changes in soleus muscle, evident at 16 months of age

impaired skeletal muscle contractility ( J:219616 )

• significantly reduced force development in explanted soleus muscles subjected to twitch and tetanic force recordings relative to wild-type controls

progressive muscle weakness ( J:219616 )

• progressive skeletal muscle weakness

myopathy ( J:219616 )

• progressive skeletal muscle myopathy with an age-related increase in the extent of degenerative changes in soleus muscle tissue, including increased endomysial connective tissue, rounding of muscle fibers, pathological fiber size variations, centralization of myonuclei, and degenerating muscle fibers

• similar myopathic changes are detected in the diaphragm but not in gastrocnemius or quadriceps femoris muscles

decreased grip strength ( J:219616 )

• significant reduction in the 4-paw grip strength at 19 months of age relative to wild-type controls

• severely poor performance in the wire hanging test

cardiac fibrosis ( J:219616 )

• increased connective tissue in cardiac muscle at 3 months of age, more prominent than in heterozygotes

decreased cardiac stroke volume ( J:219616 )

• significantly reduced cardiac stroke volume at 2 years of age

decreased cardiac muscle contractility ( J:219616 )

• significantly reduced ejection fraction at 2 years of age

• decreased myocardial contractility (dP/dtmax value) at 1 year of age

ventricular tachycardia ( J:219616 )

• increased numbers of episodes with ventricular tachycardias (VTs)

• ventricular stimulations lead to a significant increase in the number of VT episodes

irregular heartbeat ( J:219616 )

• arrhythmias

atrial fibrillation ( J:219616 )

• increased numbers of episodes with atrial fibrillation

• long-lasting (>1 min) AF-episodes

ventricular premature beat ( J:219616 )

• significantly increased number of polymorphic premature ventricular contractions (PVCs) during physical stress (10 min swimming exercise) at 6 months of age

abnormal impulse conducting system conduction ( J:219616 )

• conduction defects

atrioventricular block ( J:219616 )

• higher grade AV blocks under conditions of stress

• 2nd and 3rd degree AV blocks, never observed in wild-type controls

abnormal heart electrocardiography waveform feature ( J:219616 )

• long-term telemetric baseline electrocardiography recordings revealed atrial and ventricular extrasystoles at 6 months of age

prolonged HV interval ( J:219616 )

• significantly prolonged HV intervals

• however, supra-Hisian AV nodal conductance (AH interval) is normal

sinoatrial block ( J:219616 )

• higher grade sino-atrial blocks under conditions of stress