Phenotypes Associated with This Genotype

Genotype
MGI:5905901

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetORo1-lacZ)3Conk/0
• Genetic Background: FVB.Cg-Tg(Myh6-tTA)6Smbf Tg(tetORo1-lacZ)3Conk

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

mortality/aging

premature death ( J:107363 )

• mice weaned from doxycycline (DOX) at 8 weeks of age die within 16 weeks of DOX removal

cardiovascular system

abnormal myocardium layer morphology ( J:107363 )

• after 2 weeks of DOX removal, a cellular infiltrate is seen in the myocardium

myocardial fiber disarray ( J:107363 )

• after 4 weeks of DOX removal, patchy myocyte disarray is seen in the myocardium

increased heart ventricle size ( J:107363 )

• enlarged ventricular chamber size in mice weaned off DOX

thin ventricular wall ( J:107363 )

• decrease in ventricular wall thickness when weaned off DOX

cardiac fibrosis ( J:107363 )

• collagen deposition is seen in the myocardium after 4 weeks of DOX removal and maximal replacement of the myocardium with collagen is seen after 8 weeks of DOX removal

dilated cardiomyopathy ( J:107363 )

• mice develop dilated cardiomyopathy in systole and diastole when weaned off DOX

• however, cardiac hypertrophy is not seen

decreased cardiac muscle contractility ( J:107363 )

• rates of muscle contraction and relaxation are prolonged in mice after 8 weeks of DOX removal

• the end-systolic diameter is 50% greater and aortic peak flow velocity and left ventricle fractional shortening are 40% lower than in controls in mice after 8 weeks of DOX removal

decreased heart ventricle muscle contractility ( J:107363 )

decreased heart left ventricle muscle contractility ( J:107363 )

• mice show impaired left ventricular fractional shortening and aortic peak flow velocity in mice after 8 weeks of DOX removal

decreased heart right ventricle muscle contractility ( J:107363 )

• after 8 weeks of DOX removal, absolute force of right ventricular papillary muscle is 50% lower than in controls

abnormal cardiac muscle relaxation ( J:107363 )

• rates of muscle contraction and relaxation are prolonged in mice after 8 weeks of DOX removal

irregular heartbeat ( J:107363 )

• cardiac arrhythmias develop in mice that are weaned off DOX

prolonged QRS complex duration ( J:107363 )

• mice weaned off DOX exhibit wide QRS complexes on the days before death indicating ventricular conduction delay

• treatment with PTX results in a 90% reduction in the number of prolonged QRS events

growth/size/body

cachexia ( J:107363 )

• 8 of 14 mice develop clinical distress just before death, with labored breathing, rough hair coat, complete inactivity, failure to eat or drink, and fluid retention

homeostasis/metabolism

dehydration ( J:107363 )

• some mice show signs of dehydration caused by lack of fluid intake before death

edema ( J:107363 )

ascites ( J:107363 )

pleural effusion ( J:107363 )

muscle

abnormal myocardium layer morphology ( J:107363 )

• after 2 weeks of DOX removal, a cellular infiltrate is seen in the myocardium

myocardial fiber disarray ( J:107363 )

• after 4 weeks of DOX removal, patchy myocyte disarray is seen in the myocardium

dilated cardiomyopathy ( J:107363 )

• mice develop dilated cardiomyopathy in systole and diastole when weaned off DOX

• however, cardiac hypertrophy is not seen

decreased cardiac muscle contractility ( J:107363 )

• rates of muscle contraction and relaxation are prolonged in mice after 8 weeks of DOX removal

• the end-systolic diameter is 50% greater and aortic peak flow velocity and left ventricle fractional shortening are 40% lower than in controls in mice after 8 weeks of DOX removal

decreased heart ventricle muscle contractility ( J:107363 )

decreased heart left ventricle muscle contractility ( J:107363 )

• mice show impaired left ventricular fractional shortening and aortic peak flow velocity in mice after 8 weeks of DOX removal

decreased heart right ventricle muscle contractility ( J:107363 )

• after 8 weeks of DOX removal, absolute force of right ventricular papillary muscle is 50% lower than in controls

abnormal cardiac muscle relaxation ( J:107363 )

• rates of muscle contraction and relaxation are prolonged in mice after 8 weeks of DOX removal

respiratory system

pleural effusion ( J:107363 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:107363