Phenotypes Associated with This Genotype

Genotype
MGI:5905421

• Allelic Composition: Egfr^wa2/Egfr^wa2
• Genetic Background: involves: C57BL/6

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

cardiovascular system

abnormal aorta morphology ( J:241813 )

• aortic enlargement at 1.5 months of age

• aortic diameters at the level of the sinuses of Valsalva and at the level of the proximal ascending aorta are increased at all ages

abnormal myocardial fiber morphology ( J:241813 )

• myocardial transverse tubule organization is disrupted at 12 months of age but not at 1.5 and 3 months

abnormal heart left ventricle morphology ( J:241813 )

• left ventricle mass, indexed to body mass, is elevated at 1.5, 6, and 12 months of age

• pioglitazone treatment has no effect on left ventricle mass

abnormal aortic valve morphology ( J:241813 )

• aortic valve collagen levels are normal at 1.5 months of age but are increased at 6 and 12 months of age

• lipid levels are increased in aortic valves at 6 and 12 months of age but not at 1.5 months

• levels of proteoglycan in the aortic valve are elevated at 1.5, 6, and 12 months of age

• alpha-smooth muscle actin levels are elevated in aortic valves at 6 and 12 months of age but not at 1.5 months, indicating transdifferentiation of valve interstitial cells from a quiescent state to a profibrotic state

• intact versican is increased while cleaved versican is reduced in aortic valves at 6 months of age indicating increased levels of total proteoglycan

• however, levels of biglycan are normal

• pioglitazone treatment has no effect on collagen levels, on aortic valve lipid levels, on aortic valve alpha-smooth muscle actin levels, or on intact or cleaved versican levels

aortic valve stenosis ( J:241813 )

• 3 of 55 mice show an aortic cup separation of <0.66 mm, indicating a low level of aortic stenosis

• aortic cusp separation is normal in most mice and aortic cusp movement is symmetrical at all ages

calcified aortic valve ( J:241813 )

• aortic valve calcification is increased at 6 and 12 months of age but not at 1.5 months

• marker analysis indicates osteogenic transformation in the aortic valve at 6 and 12 months of age but not at 1.5 months

• pioglitazone treatment reduces valve calcification

increased heart left ventricle size ( J:241813 )

• left ventricle chamber enlargement at 1.5, 6, and 12 months of age

heart left ventricle hypertrophy ( J:241813 )

• left ventricle hypertrophy at 1.5 and 3 months of age, at a time when left ventricle systolic function is normal

cardiac fibrosis ( J:241813 )

• fibrosis is evident in the myocardium at 12 months of age

increased cardiac stroke volume ( J:241813 )

• left ventricle stroke volume is increased at 1.5, 6, and 12 months of age

• however, stroke volume is not increased in the 30% of mice that do not have aortic regurgitation at 1.5 months of age

• pioglitazone treatment has no effect on left ventricle stroke volume

decreased heart ventricle muscle contractility ( J:241813 )

decreased heart left ventricle muscle contractility ( J:241813 )

• left ventricle ejection fraction is decreased by 12 months of age but not at 1.5 and 6 months of age

• by 12 months of age, a trend toward greater left ventricular dilation and lower left ventricle ejection fraction in females than in males

decreased heart right ventricle muscle contractility ( J:241813 )

• right ventricle ejection fraction is decreased at 6 months of age

abnormal heart valve physiology ( J:241813 )

• an increase in apoptosis in the aortic valve is seen at 6 and 12 months of age, but not at 1.5 months

• elevation of transvalvular gradients in aortic valves

• treatment with pioglitazone prevents increases in apoptosis

aortic valve regurgitation ( J:241813 )

• prevalence of moderate or severe aortic regurgitation is 70%, 81%, and 73% at 1.5, 6, and 12 months of age, respectively

• all mice with aortic stenosis also have severe aortic regurgitation with diastolic prolapse of more than or equal to 1 valve cusps into the left ventricular outflow tract

• however, mitral regurgitation is absent

• pioglitazone treatment has no effect on prevalence of aortic regurgitation

increased pulse pressure ( J:241813 )

• increase in transvalvular gradients associated with increased aortic pulse pressure

muscle

abnormal myocardial fiber morphology ( J:241813 )

• myocardial transverse tubule organization is disrupted at 12 months of age but not at 1.5 and 3 months

heart left ventricle hypertrophy ( J:241813 )

• left ventricle hypertrophy at 1.5 and 3 months of age, at a time when left ventricle systolic function is normal

decreased heart ventricle muscle contractility ( J:241813 )

decreased heart left ventricle muscle contractility ( J:241813 )

• left ventricle ejection fraction is decreased by 12 months of age but not at 1.5 and 6 months of age

• by 12 months of age, a trend toward greater left ventricular dilation and lower left ventricle ejection fraction in females than in males

decreased heart right ventricle muscle contractility ( J:241813 )

• right ventricle ejection fraction is decreased at 6 months of age

growth/size/body

heart left ventricle hypertrophy ( J:241813 )

• left ventricle hypertrophy at 1.5 and 3 months of age, at a time when left ventricle systolic function is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
aortic valve disease		DOID:62		J:241813