Phenotypes Associated with This Genotype

Genotype
MGI:6102946

• Allelic Composition: Lrp1^tm2Her/Lrp1^tm2Her; Tg(Tagln-cre)1Her/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

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

cardiovascular system

abnormal ascending aorta morphology ( J:209752 )

• ascending aortas are characterized by increased cell nuclei and fractured elastic laminae and show progressive intra-lamellar thickening, extracellular matrix deposition, and cellular disorganization

• medial layers of the ascending aorta exhibits increased cellular and intracellular accumulation of connective tissue growth factor

dilated ascending aorta ( J:209752 )

• dilated ascending aortas in mice older than 36 weeks of age

dilated aorta bulb ( J:209752 )

• dilation of aortic roots is seen beginning at 16 weeks of age and progresses with age

abnormal coronary artery morphology ( J:209752 )

• coronary arteries within the left ventricle show accumulation of collagen within the tunica media and adventitia

perivascular fibrosis ( J:209752 )

• increase in perivascular fibrosis with outward extension of fibrotic lesions surrounding intramural coronary arteries in 48 week old mice

• extensive and continuous fibrotic lesions tracts extending outward from coronary arteries are sporadically seen in ventricle walls

abnormal myocardial fiber morphology ( J:209752 )

• increase in myocyte longitudinal area in parenchymal regions of the left ventricle free wall in 48 week old mice

enlarged heart ( J:209752 )

• increase in heart size in mice older than 36 weeks of age

increased heart weight ( J:209752 )

• heart weight to body weight ratios are increased throughout the age range from 16 to 70 weeks of age

increased heart left ventricle size ( J:209752 )

• left ventricle enlargement in 48 week old mice

dilated heart left ventricle ( J:209752 )

cardiac interstitial fibrosis ( J:209752 )

• interstitial fibrosis in intramural coronary arteries of left ventricle free wall and extensive fibrosis in left ventricle papillary muscles

• however, no pericellular fibrosis is seen

dilated cardiomyopathy ( J:209752 )

decreased cardiac muscle contractility ( J:209752 )

• a 38% reduction in fractional shortening and 43% reduction in ejection fraction

abnormal heart echocardiography feature ( J:209752 )

• echocardiography shows a reduction in systolic function, with a 38% reduction in fractional shortening, 43% reduction in ejection fraction, and 68% increase in left ventricular diameter in 36 week old mice

aortic valve regurgitation ( J:209752 )

• mice show age-dependent increase in incidence of aortic insufficiency, with all mice showing it at 30 weeks of age

increased pulse pressure ( J:209752 )

• 24 week old mice exhibit a 44% higher pulse pressure than controls

• captopril treatment reduces pulse pressure to levels seen in untreated control mice

decreased systemic arterial diastolic blood pressure ( J:209752 )

• 16% reduction in diastolic pressure in 24 week old mice

• however, systolic blood pressure is normal

muscle

abnormal myocardial fiber morphology ( J:209752 )

• increase in myocyte longitudinal area in parenchymal regions of the left ventricle free wall in 48 week old mice

dilated cardiomyopathy ( J:209752 )

decreased cardiac muscle contractility ( J:209752 )

• a 38% reduction in fractional shortening and 43% reduction in ejection fraction

growth/size/body

enlarged heart ( J:209752 )

• increase in heart size in mice older than 36 weeks of age

increased heart weight ( J:209752 )

• heart weight to body weight ratios are increased throughout the age range from 16 to 70 weeks of age

cellular

cardiac interstitial fibrosis ( J:209752 )

• interstitial fibrosis in intramural coronary arteries of left ventricle free wall and extensive fibrosis in left ventricle papillary muscles

• however, no pericellular fibrosis is seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiomyopathy		DOID:0050700		J:209752