Phenotypes Associated with This Genotype

Genotype
MGI:7261455

• Allelic Composition: Cxcr4^tm2Yzo/Cxcr4^tm2Yzo; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

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

mortality/aging

premature death ( J:289614 )

• most mice die between 12-14 months of age

cardiovascular system

perivascular fibrosis ( J:289614 )

• at 6 months, but not 2 months, mice show progressive interstitial/perivascular fibrosis

abnormal heart morphology ( J:289614 )

• hearts from 5-month-old mice have a higher number of mitochondria and these mitochondria are smaller than in controls

• however, stroke volume and cardiac output are normal and heart rate is not significantly affected

abnormal myocardial fiber morphology ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

increased heart weight ( J:289614 )

• by 6 months of age, mice have a 15% increase in heart weight to body weight ratio and a 50% increase by 12 months of age

cardiac hypertrophy ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

• 4-month-old mice show elevated levels of atrial natriuretic factor (ANF), a maker of cardiac hypertrophy

cardiac interstitial fibrosis ( J:289614 )

• at 6 months, but not 2 months, mice show progressive interstitial/perivascular fibrosis

decreased ventricle muscle contractility ( J:289614 )

• 12-month-old mice exhibit a 3-fold decline in the maximum rate of change in left ventricular pressure (dp/dt max) and a more than 2.5-fold decline in ejection fraction

• 4-month-old mice exhibit a 2.5-fold decrease in contractility and a significant decrease in ejection fraction

decreased left ventricle systolic pressure ( J:289614 )

• mice show an increase in left ventricular end-diastolic volume and an increase in end-systolic volume, indicating a decline in systolic pressures over time

cardiomyopathy ( J:289614 )

• mice develop progressive cardiomyopathy, showing mild cardiomyopathy as early as 4 months of age

congestive heart failure ( J:289614 )

• progressive cardiac dysfunction leads to clinical hear failure by 12 months of age

growth/size/body

increased heart weight ( J:289614 )

• by 6 months of age, mice have a 15% increase in heart weight to body weight ratio and a 50% increase by 12 months of age

cardiac hypertrophy ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

• 4-month-old mice show elevated levels of atrial natriuretic factor (ANF), a maker of cardiac hypertrophy

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:289614 )

• mice are more sensitive to catecholamine exposure via an acute isoproterenol challenge, showing a greater increase in ejection fraction and dp/dt max; mice show a robust response to isoproterenol and overcome their baseline deficits to eventually reach control levels, however the effect is only transient and cardiac function goes back to baseline within minutes

muscle

abnormal myocardial fiber morphology ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

decreased ventricle muscle contractility ( J:289614 )

• 12-month-old mice exhibit a 3-fold decline in the maximum rate of change in left ventricular pressure (dp/dt max) and a more than 2.5-fold decline in ejection fraction

• 4-month-old mice exhibit a 2.5-fold decrease in contractility and a significant decrease in ejection fraction

cardiomyopathy ( J:289614 )

• mice develop progressive cardiomyopathy, showing mild cardiomyopathy as early as 4 months of age

cellular

cardiac interstitial fibrosis ( J:289614 )

• at 6 months, but not 2 months, mice show progressive interstitial/perivascular fibrosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiomyopathy		DOID:0050700		J:289614
congestive heart failure		DOID:6000		J:289614