Phenotypes Associated with This Genotype

Genotype
MGI:2661730

• Allelic Composition: Ace2^tm1Pngr/Y
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

cardiovascular system

cardiac hypertrophy ( J:124548 )

♂ • development of cardiomyopathy is associated with eccentric hypertrophy as indicated by increased left ventricle weight normalized to tibial length or body weight

♂ • hearts show upregulation of hypertrophic disease markers ANF and BNP

decreased heart left ventricle wall thickness ( J:77232 )

♂ • slight thinning of the left ventricular wall resulting in mild dilation, 6 months of age

dilated heart ventricle ( J:124548 )

♂ • ventricular dilation at 6 and 12 months of age

dilated heart left ventricle ( J:124548 )

♂ • progressive left ventricular dilation and reduced systolic function with increasing age

abnormal cardiovascular system physiology ( J:124548 )

♂ • age-dependent and progressive decline in cardiac function

dilated cardiomyopathy ( J:124548 )

♂ • development of cardiomyopathy is associated with eccentric hypertrophy as indicated by increased left ventricle weight normalized to tibial length or body weight

♂ • young mice treated with the specific AT1 receptor blocker, irbesartan, until 12 months of age prevents the development of dilated cardiomyopathy at 6 months and persists until 12 months of age

decreased cardiac muscle contractility ( J:77232 , J:124548 )

♂ • more severe at 6 months of age than at 3 months of age (J:77232)

♂ • more severe in 6 month old males than in age matched female mutant mice (J:77232)

♂ • decrease in fractional shortening and velocity of circumferential shortening corrected for heart rate, decreased peak aortic velocity corrected for heart rate (J:124548)

♂ • rightward displacement of the pressure-volume curve indicating reduced systolic function (J:124548)

abnormal heart echocardiography feature ( J:124548 )

♂ • echocardiography indicates increased left ventricular end diastolic and systolic dimension, decreased fractional shortening, decreased velocity of circumferential shortening corrected for heart rate, decreased peak aortic velocity corrected for heart rate, increased left ventricle end diastolic pressure, and decreased maximum and minimum first derivative of the left ventricle pressure (+dP/dt and dP/dt)

increased left ventricle diastolic pressure ( J:124548 )

♂ • increase in left ventricle end diastolic pressure

hypotension ( J:77232 )

♂ • reduced blood pressure observed at 6 months of age

♂ • blood pressure was normal at 3 months of age

congestive heart failure ( J:124548 )

♂

heart inflammation ( J:124548 )

♂ • 4-fold increase in neutrophil infiltration in the myocardium of aged mice

♂ • however, no macrophage infiltration into the myocardium is seen

♂ • treatment with irbesartan prevents neutrophil infiltration in the myocardium

growth/size/body

cardiac hypertrophy ( J:124548 )

♂ • development of cardiomyopathy is associated with eccentric hypertrophy as indicated by increased left ventricle weight normalized to tibial length or body weight

♂ • hearts show upregulation of hypertrophic disease markers ANF and BNP

cellular

oxidative stress ( J:124548 )

♂ • myocardial aldehyde levels are increased in mice indicating chronic myocardial oxidative damage

♂ • treatment with irbesartan normalizes myocardial aldehyde levels

homeostasis/metabolism

abnormal cytokine level ( J:124548 )

♂ • increase in expression of inflammatory cytokines, IL-1beta, IL-6, and MCP-1 in aged mice

♂ • treatment with irbesartan prevents increased expression of inflammatory cytokines

increased NAD(P)H oxidase activity ( J:124548 )

♂ • NADPH oxidase activity is increase in the left ventricle of 6 month old mice

♂ • mice treated with irbesartan to block AT1 suppresses the increase in NADPH oxidase activity

muscle

dilated cardiomyopathy ( J:124548 )

♂ • development of cardiomyopathy is associated with eccentric hypertrophy as indicated by increased left ventricle weight normalized to tibial length or body weight

♂ • young mice treated with the specific AT1 receptor blocker, irbesartan, until 12 months of age prevents the development of dilated cardiomyopathy at 6 months and persists until 12 months of age

decreased cardiac muscle contractility ( J:77232 , J:124548 )

♂ • more severe at 6 months of age than at 3 months of age (J:77232)

♂ • more severe in 6 month old males than in age matched female mutant mice (J:77232)

♂ • decrease in fractional shortening and velocity of circumferential shortening corrected for heart rate, decreased peak aortic velocity corrected for heart rate (J:124548)

♂ • rightward displacement of the pressure-volume curve indicating reduced systolic function (J:124548)

immune system

heart inflammation ( J:124548 )

♂ • 4-fold increase in neutrophil infiltration in the myocardium of aged mice

♂ • however, no macrophage infiltration into the myocardium is seen

♂ • treatment with irbesartan prevents neutrophil infiltration in the myocardium

abnormal cytokine level ( J:124548 )

♂ • increase in expression of inflammatory cytokines, IL-1beta, IL-6, and MCP-1 in aged mice

♂ • treatment with irbesartan prevents increased expression of inflammatory cytokines

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congestive heart failure		DOID:6000		J:124548