Phenotypes Associated with This Genotype

Genotype
MGI:4947945

• Allelic Composition: Efemp2^tm1.1Hiya/Efemp2^tm1.2Hiya; Tg(Tagln-cre)1Her/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

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

mortality/aging

premature death ( J:170883 )

• mice die at 2 months of age

cardiovascular system

abnormal aorta wall morphology ( J:213282 )

• increase in proliferation of aorta vessel wall at 1 month of age

• vessel area is increased in the aorta

abnormal aorta tunica media morphology ( J:170883 )

• increased in thickness

abnormal aorta elastic fiber morphology ( J:170883 )

• disorganized

abnormal aorta smooth muscle morphology ( J:213282 )

• smooth muscle cells of the aorta are abnormal by P14 and their proliferation extends throughout the medial layer

• hyperproliferation and disarray of smooth muscle cells in the ascending aorta wall at 3 months of age

abnormal ascending aorta morphology ( J:170883 , J:213282 )

• focal lesions with thickened aortic wall (J:170883)

• increased collagen fibers (J:170883)

• cellularity in the aorta is increased by P7, especially in the subendothelial layer and near the adventitia (J:213282)

ascending aorta aneurysm ( J:170883 , J:213282 )

• captopril, an ACE inhibitor, or losartan treatment of pregnant females and continued until 3 months of age, completely prevents aneurysm formation and hyperproliferaton and disarray of smooth muscle cells in the aortic wall, however amount of collagen is decreased, and elastic fibers remain irregular (J:213282)

• administration of losartan starting at P7 completely prevents aneurysms, however administration from P30 to P90 does not prevent aneurysms (J:213282)

• however, propranolol, a beta-adrenergic receptor blocker, treatment shows modest inhibitory effects on aneurysm formation (J:213282)

dilated ascending aorta ( J:213282 )

• slight dilatation of the ascending aorta is seen at P14

abnormal vascular smooth muscle morphology ( J:170883 )

• vascular smooth muscle cells exhibit defective differentiation compared to in wild-type mice

increased pulse pressure ( J:213282 )

• pulse pressures are increased 50%

• captopril treatment decreases this increase in pulse pressure

decreased systemic arterial diastolic blood pressure ( J:213282 )

• mice show a trend toward lower average diastolic pressures

• captopril treatment decreases systolic blood pressures about 20% in mutants, however losartan or propranolol have no effect on blood pressure

abnormal blood vessel physiology ( J:213282 )

• compliance of the ascending aorta is decreased 60-80% in the middle-to high-pressure range (75-175 mmHg), indicating that the vessel wall is stiffer

• treatment with losartan or captopril does not completely reverse the increase in vessel wall stiffness

muscle

abnormal vascular smooth muscle morphology ( J:170883 )

• vascular smooth muscle cells exhibit defective differentiation compared to in wild-type mice

abnormal aorta smooth muscle morphology ( J:213282 )

• smooth muscle cells of the aorta are abnormal by P14 and their proliferation extends throughout the medial layer

• hyperproliferation and disarray of smooth muscle cells in the ascending aorta wall at 3 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
aortic aneurysm		DOID:3627		J:213282