Phenotypes associated with this allele

• Allele Symbol: Efemp2^tm1.2Hiya
• Allele Name: targeted mutation 1.2, Hiromi Yanagisawa
• Allele ID: MGI:4947939
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Efemp2^tm1.2Hiya/Efemp2^tm1.2Hiya	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:4947947
cn2	Agtr2^tm1Tin/Y Efemp2^tm1.1Hiya/Efemp2^tm1.2Hiya Tg(Tagln-cre)1Her/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * SJL	MGI:5585151
cn3	Agtr1a^tm1Unc/Agtr1a^tm1Unc Efemp2^tm1.1Hiya/Efemp2^tm1.2Hiya Tg(Tagln-cre)1Her/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * SJL	MGI:5585152
cn4	Efemp2^tm1.1Hiya/Efemp2^tm1.2Hiya Tg(Tagln-cre)1Her/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:4947945
cn5	Efemp2^tm1.1Hiya/Efemp2^tm1.2Hiya Tg(Tek-cre)1Ywa/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:4947946

Genotype
MGI:4947947

hm1

• Allelic Composition: Efemp2^tm1.2Hiya/Efemp2^tm1.2Hiya
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

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

mortality/aging

perinatal lethality, complete penetrance ( J:170883 )

• mice die in or after parturition due to ascending aorta aneurysm rupture

cardiovascular system

abnormal aorta tunica media morphology ( J:170883 )

• degenerative

abnormal aorta elastic fiber morphology ( J:170883 )

• aortas exhibit degeneration and decrease of the elastic fiber compared to in wild-type mice

ascending aorta aneurysm ( J:170883 )

• mice die in or after parturition due to ascending aorta aneurysm rupture

abnormal vascular smooth muscle morphology ( J:170883 )

• vascular smooth muscle cell are immature with round nuclei unlike in wild-type mice

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

vascular smooth muscle hyperplasia ( J:170883 )

• E17.5 and E18.5

increased vascular endothelial cell apoptosis ( J:170883 )

increased vascular endothelial cell proliferation ( J:170883 )

abnormal vascular smooth muscle physiology ( J:170883 )

• mice exhibit increased apoptosis of vascular smooth muscle cells compared with wild-type mice

increased vascular smooth muscle cell proliferation ( J:170883 )

• mice exhibit increased proliferation of vascular smooth muscle cells compared with wild-type mice

muscle

abnormal vascular smooth muscle morphology ( J:170883 )

• vascular smooth muscle cell are immature with round nuclei unlike in wild-type mice

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

vascular smooth muscle hyperplasia ( J:170883 )

• E17.5 and E18.5

abnormal vascular smooth muscle physiology ( J:170883 )

• mice exhibit increased apoptosis of vascular smooth muscle cells compared with wild-type mice

increased vascular smooth muscle cell proliferation ( J:170883 )

• mice exhibit increased proliferation of vascular smooth muscle cells compared with wild-type mice

cellular

increased vascular endothelial cell apoptosis ( J:170883 )

increased vascular endothelial cell proliferation ( J:170883 )

increased vascular smooth muscle cell proliferation ( J:170883 )

• mice exhibit increased proliferation of vascular smooth muscle cells compared with wild-type mice

Genotype
MGI:5585151

cn2

• Allelic Composition: Agtr2^tm1Tin/Y; Efemp2^tm1.1Hiya/Efemp2^tm1.2Hiya; Tg(Tagln-cre)1Her/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * SJL

cardiovascular system

abnormal aorta smooth muscle morphology ( J:213282 )

• hyperproliferation and disarray of aorta smooth muscle cells at 3 months of age

increased aorta wall thickness ( J:213282 )

• the medium of the aortic wall is thicker than in single Agtr2 mutants, with hyperproliferation and disarray of smooth muscle cells at 3 months of age

ascending aorta aneurysm ( J:213282 )

• mice develop aneurysms

• treatment with losartan completely prevents aneurysms

muscle

abnormal aorta smooth muscle morphology ( J:213282 )

• hyperproliferation and disarray of aorta smooth muscle cells at 3 months of age

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

Genotype
MGI:5585152

cn3

• Allelic Composition: Agtr1a^tm1Unc/Agtr1a^tm1Unc; Efemp2^tm1.1Hiya/Efemp2^tm1.2Hiya; Tg(Tagln-cre)1Her/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * SJL

cardiovascular system

increased aorta wall thickness ( J:213282 )

• aortic wall is thicker at 3 months of age compared to single Agtr1a homozygotes

Genotype
MGI:4947945

cn4

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

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

Genotype
MGI:4947946

cn5

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

normal phenotype

no abnormal phenotype detected ( J:170883 )

• mice are indistinguishable from wild-type mice