Phenotypes Associated with This Genotype

Genotype
MGI:4818928

• Allelic Composition: Dnm1l^Py/Dnm1l⁺
• Genetic Background: involves: BALB/cAnNCrl * C3H/HeH

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

Dnm1l^Py/Dnm1l⁺ mice exhibit dilated cardiomyopathy

growth/size/body

increased body size ( J:161510 )

• rapid size increase

• normal body weight at 11 weeks old

cardiovascular system

visceral vascular congestion ( J:161510 )

liver vascular congestion ( J:161510 )

• hepatic congestion at the time of overt CHF

pulmonary vascular congestion ( J:161510 )

• pulmonary congestion at the time of appearance of overt CHF

abnormal heart morphology ( J:161510 )

abnormal myocardial fiber mitochondrial morphology ( J:161510 )

• decrease in mitochondrial DNA content in some mutant hearts at the time of appearance of overt CHF

• slightly smaller average size of a mitochondrion in mutant hearts at 10 weeks of age

increased myocardial fiber size ( J:161510 )

• cardiomyocyte hypertrophy

thin myocardium ( J:161510 )

• biatrial and biventricular thinning

cardiac interstitial fibrosis ( J:161510 )

• interstitial fibrosis with increased collagen deposition in heart

• increased collagenous tissue by almost 7-fold in hearts of terminal mice

dilated heart ( J:161510 )

• grossly dilated heart by the time of overt congestive heart failure (CHF)

• biatrial and biventricular dilatation

dystrophic cardiac calcinosis ( J:161510 )

• prominent cardiac calcification

abnormal cardiovascular system physiology ( J:161510 )

decreased ventricle muscle contractility ( J:161510 )

• contractility is 40% lower than in littermate controls at approximately 2 weeks before overt clinical signs of CHF become evident

• a reduced contractile reserve and a severely impaired maximum contractility under conditions of maximal b-adrenergic stimulation with dobutamine

abnormal cardiac muscle relaxation ( J:161510 )

• impaired relaxation with dP/dt min 46% lower than controls

• significant prolongation of the isovolumetric constant of relaxation (Tau)

abnormal heart ventricle pressure ( J:161510 )

decreased left ventricle systolic pressure ( J:161510 )

• left ventricular (LV) end-systolic pressure is 22 mmHg lower than in littermate controls at approximately 2 weeks before overt clinical signs of CHF become evident

increased left ventricle diastolic pressure ( J:161510 )

• significantly elevated LV end-diastolic pressure

decreased mean systemic arterial blood pressure ( J:161510 )

• significantly reduced aortic blood pressures

congestive heart failure ( J:161510 )

• exhibit features of congestive heart failure, i.e. dialted hearts, pleural effusions, substantial ascites and subcutaneous edema

• Background Sensitivity: the median age of onset is 91 days for females and 83 days for males

• inherited in an autosomal dominant fashion

• no obvious anatomical abnormalities in embryonic hearts

homeostasis/metabolism

increased circulating alanine transaminase level ( J:161510 )

• increased plasma levels of liver enzymes alanine aminotransferase

increased circulating aspartate transaminase level ( J:161510 )

• increased plasma levels of liver enzymes aspartate aminotransferase

skin edema ( J:161510 )

• subcutaneous edema

ascites ( J:161510 )

• substantial ascites

pleural effusion ( J:161510 )

• pleural effusion in some CHF mutant mice

abnormal metabolism ( J:161510 )

• reductions in mitochondrial metabolic intermediates or accessory molecules e.g. succinate, malate, fumarate, pyruvate, creatine, glucose, AMP and adenosine in mutant hearts

• increases in the amino acids glycine and proline in mutant hearts

behavior/neurological

abnormal pilomotor reflex ( J:161510 )

• piloerection

cellular

cardiac interstitial fibrosis ( J:161510 )

• interstitial fibrosis with increased collagen deposition in heart

• increased collagenous tissue by almost 7-fold in hearts of terminal mice

abnormal mitochondrial morphology ( J:161510 )

• highly elongated mitochondria in MEFs and neonatal mouse skin fibroblasts

• normal total mitochondrial volume

abnormal myocardial fiber mitochondrial morphology ( J:161510 )

• decrease in mitochondrial DNA content in some mutant hearts at the time of appearance of overt CHF

• slightly smaller average size of a mitochondrion in mutant hearts at 10 weeks of age

abnormal peroxisome morphology ( J:161510 )

• highly elongated peroxisomes in neonatal mouse skin fibroblasts

abnormal cellular respiration ( J:161510 )

• a slight reduction trend in the overall level of mitochondrial citrate synthase activity in mutant hearts at 10 weeks of age

• a dramatic, approximately 50%, reduction in myocardial ATP and total adenine nucleotide (TAN) levels

abnormal mitochondrial ATP synthesis coupled electron transport ( J:161510 )

• a reduction for cytochrome c oxidase (Complex IV) activities in mutant hearts at 12 weeks of age

• diminished myocellular succinate dehydrogenase activity in mutant hearts at 12 weeks of age

liver/biliary system

liver vascular congestion ( J:161510 )

• hepatic congestion at the time of overt CHF

respiratory system

pulmonary vascular congestion ( J:161510 )

• pulmonary congestion at the time of appearance of overt CHF

pleural effusion ( J:161510 )

• pleural effusion in some CHF mutant mice

tachypnea ( J:161510 )

• shallow rapid breathing

muscle

abnormal myocardial fiber mitochondrial morphology ( J:161510 )

• decrease in mitochondrial DNA content in some mutant hearts at the time of appearance of overt CHF

• slightly smaller average size of a mitochondrion in mutant hearts at 10 weeks of age

increased myocardial fiber size ( J:161510 )

• cardiomyocyte hypertrophy

thin myocardium ( J:161510 )

• biatrial and biventricular thinning

decreased ventricle muscle contractility ( J:161510 )

• contractility is 40% lower than in littermate controls at approximately 2 weeks before overt clinical signs of CHF become evident

• a reduced contractile reserve and a severely impaired maximum contractility under conditions of maximal b-adrenergic stimulation with dobutamine

abnormal cardiac muscle relaxation ( J:161510 )

• impaired relaxation with dP/dt min 46% lower than controls

• significant prolongation of the isovolumetric constant of relaxation (Tau)

integument

skin edema ( J:161510 )

• subcutaneous edema

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:161510