Phenotypes associated with this allele

• Allele Symbol: Tg(Cdh5-cre/ERT2)1Rha
• Allele Name: transgene insertion 1, Ralf H Adams
• Allele ID: MGI:3848982
• Summary: 37 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gpr182^tm2c(KOMP)Wtsi/Gpr182^tm2c(KOMP)Wtsi Tg(Cdh5-cre/ERT2)1Rha/0	B6.Cg-Gpr182^tm2c(KOMP)Wtsi Tg(Cdh5-cre/ERT2)1Rha	MGI:6712273
cn2	Ccm2^tm1Mlkn/Ccm2^tm1Mlkn Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129	MGI:6279212
cn3	Dll1^tm1Mjo/Dll1^tm1Mjo Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129	MGI:3848985
cn4	Ccm2^tm1.1Etl/Ccm2^tm1Etl Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129 * C57BL/6	MGI:5297594
cn5	Ccm2^tm1Mlkn/Ccm2^tm1Mlkn Map3k3^tm1.1Mlkn/Map3k3^+ Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129 * C57BL/6NTac	MGI:6279213
cn6	Apoe^tm1Unc/Apoe^tm1Unc Nck1^tm1Paw/Nck1^tm1Paw Nck2^tm3Paw/Nck2^tm3Paw Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:7316557
cn7	Nus1^tm1.1Qrm/Nus1^tm1.1Qrm Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129P2/OlaHsd * C57BL/6	MGI:6361030
cn8	Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/Gt(ROSA)26Sor^+ Pfkfb3^tm1Pec/Pfkfb3^tm1Pec Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S1/Sv * 129X1/SvJ	MGI:5825525
cn9	Sox17^tm2Sjm/Sox17^tm2Sjm Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5792803
cn10	Gipc1^tm1.1Mhsi/Gipc1^tm1.1Mhsi Tg(Cdh5-cre/ERT2)1Rha/?	involves: 129S1/SvImJ * 129S4/SvJaeSor * C57BL/6	MGI:5696330
cn11	Kras^tm4Tyj/Kras^+ Tg(Cdh5-cre/ERT2)1Rha/0 Gt(ROSA)26Sor^tm14(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6NCrl * FVB	MGI:7435431
cn12	Kras^tm4Tyj/Kras^+ Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S4/SvJae * FVB	MGI:7435429
cn13	Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor^+ S1pr1^tm2Rlp/S1pr1^tm2Rlp Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S6/SvEvTac * 129X1/SvJ	MGI:5445987
cn14	Klf2^tm1Mlkn/Klf2^+ Krit1^tm1Kwhi/Krit1^tm1Kwhi Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S6/SvEvTac * C57BL/6NCrl	MGI:6279216
cn15	Krit1^tm1Kwhi/Krit1^tm1Kwhi Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S6/SvEvTac * C57BL/6NCrl	MGI:6279211
cn16	Klf2^tm1Mlkn/Klf2^tm1Mlkn Krit1^tm1Kwhi/Krit1^tm1Kwhi Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S6/SvEvTac * C57BL/6NCrl	MGI:6279217
cn17	Klf4^tm1Khk/Klf4^+ Krit1^tm1Kwhi/Krit1^tm1Kwhi Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S6/SvEvTac * C57BL/6NCrl	MGI:6279218
cn18	Krit1^tm1Kwhi/Krit1^tm1Kwhi Map3k3^tm1.1Mlkn/Map3k3^+ Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S6/SvEvTac * C57BL/6NCrl * C57BL/6NTac	MGI:6279215
cn19	Nus1^tm1Wcsa/Nus1^+ Rtn4^tm1Matl/Rtn4^tm1Matl Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S7/SvEvBrd	MGI:6361104
cn20	Mef2a^tm1.1Limm/Mef2a^tm1.1Limm Mef2c^tm1Jjs/Mef2c^tm1Jjs Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129S/SvEv * 129S6/SvEvTac	MGI:7447283
cn21	Amotl1^tm1Laho/Amotl1^tm1Laho Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor^+ Tg(Cdh5-cre/ERT2)1Rha/0	involves: 129X1/SvJ * C57BL/6	MGI:6723729
cn22	Amotl2^tm1.1Laho/Amotl2^tm1.1Laho Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6	MGI:6121065
cn23	Lypla1^tm1Sem/Lypla1^tm1Sem Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6	MGI:6514412
cn24	Amotl1^tm1Laho/Amotl1^tm1Laho Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6	MGI:6723732
cn25	Pdcd10^tm1Arte/Pdcd10^tm1Arte Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6	MGI:5297596
cn26	Krit1^tm1Arte/Krit1^tm1Arte Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6	MGI:5297595
cn27	Amotl2^tm1.1Laho/Amotl2^+ Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6	MGI:6121066
cn28	Rhoj^tm1.1Auem/Rhoj^tm1.1Auem Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6 * CBA/JNCrlj	MGI:5608673
cn29	Amotl1^tm1Laho/Amotl1^tm1Laho Tg(Cdh5-cre/ERT2)1Rha/0 Tg(MMTV-PyVT)634Mul/0	involves: C57BL/6 * FVB/N	MGI:6723730
cn30	Flvcr2^tm1.1Tda/Flvcr2^tm1.2Tda Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6J	MGI:6415692
cn31	Flvcr2^tm1.1Tda/Flvcr2^tm1.1Tda Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6J	MGI:6415689
cn32	Sdc2^tm1c(KOMP)Wtsi/Sdc2^tm1c(KOMP)Wtsi Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6J * C57BL/6N	MGI:6364849
cn33	Cyb5r1^tm1c(KOMP)Wtsi/Cyb5r1^tm1c(KOMP)Wtsi Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6N	MGI:7596537
cn34	Pfn1^tm1Foxp/Pfn1^tm1Foxp Tg(Cdh5-cre/ERT2)1Rha/0	involves: C57BL/6NTac	MGI:5470092
cn35	Cdh5^tm1Dvst/Cdh5^tm1Dvst Tg(Cdh5-cre/ERT2)1Rha/0	Not Specified	MGI:5445989
cn36	Cpt1a^tm1.1Pec/Cpt1a^tm1.1Pec Tg(Cdh5-cre/ERT2)1Rha/0	Not Specified	MGI:5771679
cn37	Nus1^tm1Wcsa/Nus1^tm1Wcsa Tg(Cdh5-cre/ERT2)1Rha/0	Not Specified	MGI:6361095

Genotype
MGI:6712273

cn1

• Allelic Composition: Gpr182^{tm2c(KOMP)Wtsi}/Gpr182^{tm2c(KOMP)Wtsi}; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: B6.Cg-Gpr182^{tm2c(KOMP)Wtsi} Tg(Cdh5-cre/ERT2)1Rha

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

hematopoietic system

abnormal hematopoietic system morphology/development ( J:305796 )

• mice show an increase in colony-forming units of hematopoietic stem/progenitors in the peripheral blood and in the spleen, paralleled by an increase in c-Kit+ cells in the spleen, following tamoxifen treatment

increased neutrophil cell number ( J:305796 )

• mice show increased levels of neutrophils and monocytes in peripheral blood following induction with tamoxifen

increased monocyte cell number ( J:305796 )

• mice show increased levels of neutrophils and monocytes in peripheral blood following induction with tamoxifen

decreased hematopoietic stem cell number ( J:305796 )

• mice show a decrease in long-term repopulating hematopoietic stem cells (LT-HSCs; CD150+CD48-CD34low LSK) in the bone marrow following induction with tamoxifen

• however, progenitor populations are not affected

homeostasis/metabolism

abnormal circulating chemokine level ( J:305796 )

• mice induced with tamoxifen show a rapid increase in plasma concentration of CXCL10, CXCL12, and CXCL13, with increase of CXCL13 more pronounced than the other two

• levels of CXCL12 and CXCL10 remain stable over a period of 20 days while CXCL13 levels continue to increase after induction

• however, no alteration in the distribution of CXCL12 is seen in the bone marrow

increased circulating CXCL10 level ( J:305796 )

• plasma concentration of CXCL10 is increased following tamoxifen treatment

immune system

increased neutrophil cell number ( J:305796 )

• mice show increased levels of neutrophils and monocytes in peripheral blood following induction with tamoxifen

increased monocyte cell number ( J:305796 )

• mice show increased levels of neutrophils and monocytes in peripheral blood following induction with tamoxifen

abnormal circulating chemokine level ( J:305796 )

• mice induced with tamoxifen show a rapid increase in plasma concentration of CXCL10, CXCL12, and CXCL13, with increase of CXCL13 more pronounced than the other two

• levels of CXCL12 and CXCL10 remain stable over a period of 20 days while CXCL13 levels continue to increase after induction

• however, no alteration in the distribution of CXCL12 is seen in the bone marrow

increased circulating CXCL10 level ( J:305796 )

• plasma concentration of CXCL10 is increased following tamoxifen treatment

Genotype
MGI:6279212

cn2

• Allelic Composition: Ccm2^tm1Mlkn/Ccm2^tm1Mlkn; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129

cardiovascular system

abnormal brain vasculature morphology ( J:250906 )

• mice injected with tamoxifen at P1 exhibit cerebral cavernous malformation lesions by P13

nervous system

abnormal brain vasculature morphology ( J:250906 )

• mice injected with tamoxifen at P1 exhibit cerebral cavernous malformation lesions by P13

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebral cavernous malformation 2		DOID:0060670	OMIM:603284	J:250906

Genotype
MGI:3848985

cn3

• Allelic Composition: Dll1^tm1Mjo/Dll1^tm1Mjo; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129

cardiovascular system

artery stenosis ( J:148902 )

• lumens of large arteries show a reduction in diameters after tamoxifen induction at E18.5, with no significant differences in arterial wall thickness

aorta stenosis ( J:148902 )

• lumen shows a reduction in diameter compared to controls

abnormal capillary branching pattern ( J:148902 )

• significant increase in capillary branch points in the skin is observed at E17.5

abnormal skin vasculature morphology ( J:148902 )

• significant increase in capillary branch points in the skin is observed at E17.5

integument

abnormal skin vasculature morphology ( J:148902 )

• significant increase in capillary branch points in the skin is observed at E17.5

Genotype
MGI:5297594

cn4

• Allelic Composition: Ccm2^tm1.1Etl/Ccm2^tm1Etl; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:177584 )

• mice injected with tamoxifen at P1 to induce recombination exhibit an median survival time of 17 days

cardiovascular system

abnormal vascular endothelial cell morphology ( J:177584 )

• endothelial cell-cell junctions are altered in cerebellar vessels of mutants injected with tamoxifen at P1

• mice injected with tamoxifen at P1 do not exhibit increased endothelial cell proliferation at P6

abnormal brain vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation (CCM) lesions within the CNS beginning at P6

• CCM lesions that develop in mutants injected with tamoxifen affect the venous bed but not the arterial compartment

• mice injected with tamoxifen at 3 weeks of age do not exhibit any gross cerebrovascular phenotype, indicating that deletion of Ccm2 at three weeks of age does not lead to cerebral cavernous malformations

• fetuses at E19.5 of pregnant mice injected with tamoxifen at E14.5, exhibit vascular anomalies on the cerebral hemispheres with irregular and tortuous rhinal cerebral veins surrounded by abnormal capillaries

• mice injected with tamoxifen at P4 show a milder phenotype compared to tamoxifen treatment at P1, with single isolated caverns located within the cerebellum without sign of hemorrhage

abnormal retina vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 show CCM vascular malformations at the periphery of the retinal vascular plexus in both eyes

• CCM malformations at the periphery of the retinas are restricted to veins and the surrounding capillaries

• mice injected with tamoxifen at P1 show a thicker vascular plexus at the venous leading edge of the retina at P7, with a 29% increase in vascular coverage compared to controls and dilated main veins by P9, with abnormal capillaries at the periphery of the vascular plexus

• by 3 weeks of age, mice injected with tamoxifen at P1 do not exhibit three distinguished vascular plexuses in the retinas as seen in controls, and the vasculature from the lesion is composed by bubble like vascular structures packed together

dilated vasculature ( J:177584 )

• cerebellar lesions of tamoxifen treated mice are composed of dilated vessels full of blood cells, and in severe cases there are signs of hemorrhage

• mice injected with tamoxifen at P1 exhibit dilation of vessels from the pial surface of the cerebellum and dilation of vessels running along the cerebellar folia at the meningeal surface corresponding to dorsal cerebellar veins

cerebellum hemorrhage ( J:177584 )

• extensive cerebral hemorrhages are seen mostly around the multiple caverns composing cerebral cavernous malformation lesions in mice before death

skin hemorrhage ( J:177584 )

• fetuses at E19.5 of pregnant mice injected with tamoxifen at E14.5, exhibit hemorrhagic skin

nervous system

abnormal brain vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation (CCM) lesions within the CNS beginning at P6

• CCM lesions that develop in mutants injected with tamoxifen affect the venous bed but not the arterial compartment

• mice injected with tamoxifen at 3 weeks of age do not exhibit any gross cerebrovascular phenotype, indicating that deletion of Ccm2 at three weeks of age does not lead to cerebral cavernous malformations

• fetuses at E19.5 of pregnant mice injected with tamoxifen at E14.5, exhibit vascular anomalies on the cerebral hemispheres with irregular and tortuous rhinal cerebral veins surrounded by abnormal capillaries

• mice injected with tamoxifen at P4 show a milder phenotype compared to tamoxifen treatment at P1, with single isolated caverns located within the cerebellum without sign of hemorrhage

cerebellum hemorrhage ( J:177584 )

• extensive cerebral hemorrhages are seen mostly around the multiple caverns composing cerebral cavernous malformation lesions in mice before death

abnormal cerebellum morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation lesions within the cerebellum beginning at P6

vision/eye

abnormal retina vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 show CCM vascular malformations at the periphery of the retinal vascular plexus in both eyes

• CCM malformations at the periphery of the retinas are restricted to veins and the surrounding capillaries

• mice injected with tamoxifen at P1 show a thicker vascular plexus at the venous leading edge of the retina at P7, with a 29% increase in vascular coverage compared to controls and dilated main veins by P9, with abnormal capillaries at the periphery of the vascular plexus

• by 3 weeks of age, mice injected with tamoxifen at P1 do not exhibit three distinguished vascular plexuses in the retinas as seen in controls, and the vasculature from the lesion is composed by bubble like vascular structures packed together

integument

skin hemorrhage ( J:177584 )

• fetuses at E19.5 of pregnant mice injected with tamoxifen at E14.5, exhibit hemorrhagic skin

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebral cavernous malformation 2		DOID:0060670	OMIM:603284	J:177584

Genotype
MGI:6279213

cn5

• Allelic Composition: Ccm2^tm1Mlkn/Ccm2^tm1Mlkn; Map3k3^tm1.1Mlkn/Map3k3⁺; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129 * C57BL/6NTac

nervous system

nervous system phenotype ( J:232707 , J:250906 )

N • tamoxifen injected mice show full rescue of cerebral cavernous malformation lesion formation (J:232707)

N • tamoxifen injected mice do not exhibit cerebral cavernous malformation lesions (J:250906)

Genotype
MGI:7316557

cn6

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Nck1^tm1Paw/Nck1^tm1Paw; Nck2^tm3Paw/Nck2^tm3Paw; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

Assessment of atherosclerosis initiation and progression in tamoxifen-treated, high-fat diet fed Apoe^tm1Unc/Apoe^tm1Unc Tg(Cdh5-cre/ERT2)1Rha/0 Nck1^tm1Paw/Nck1^tm1Paw Nck2^tm3Paw/Nck2^tm3Paw mice.

cardiovascular system

decreased susceptibility to diet-induced aortic fatty streak lesions ( J:326659 )

♂ • severity of lesions, atherosclerosis progression, and macrophage recruitment are reduced in male, but not female, following 16 weeks of a high-fat diet in tamoxifen-treated mice

♂ • however, serum lipoprotein levels are normal

immune system

decreased inflammatory response ( J:326659 )

♂ • severity of lesions, atherosclerosis progression, and macrophage recruitment are reduced in male, but not female, following 16 weeks of a high-fat diet in tamoxifen-treated mice

Genotype
MGI:6361030

cn7

• Allelic Composition: Nus1^tm1.1Qrm/Nus1^tm1.1Qrm; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

cardiovascular system

abnormal brain vasculature morphology ( J:229464 )

• E10.5 embryos from tamoxifen-treated mothers exhibit aberrant cerebral blood vessel pattering

abnormal vascular development ( J:229464 )

• E10.5 embryos from tamoxifen-treated mothers have dilated and disrupted organization of blood vessels

embryo

decreased embryo size ( J:229464 )

• E01.5 embryos are smaller in size when pregnant females are treated with tamoxifen at E8.5

growth/size/body

decreased embryo size ( J:229464 )

• E01.5 embryos are smaller in size when pregnant females are treated with tamoxifen at E8.5

nervous system

abnormal brain vasculature morphology ( J:229464 )

• E10.5 embryos from tamoxifen-treated mothers exhibit aberrant cerebral blood vessel pattering

Genotype
MGI:5825525

cn8

• Allelic Composition: Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/Gt(ROSA)26Sor⁺; Pfkfb3^tm1Pec/Pfkfb3^tm1Pec; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

cardiovascular system

abnormal retina vasculature morphology ( J:200070 )

• mice treated with tamoxifen at P1-4 show reduced vascular branching in retinal vessels at P5

• mice treated with tamoxifen at P1-4 show fewer distal sprouts with filopodia and fewer number of filopodia in the retinal vasculature

• distal sprouts have fewer side connections in the retinal vasculature of mice treated with tamoxifen at P1-4

• the radial expansion of the vascular plexus is reduced in mice treated with tamoxifen at P1-4

• vessel regression in the retina is increased in tamoxifen treated mice

cellular

decreased endothelial cell proliferation ( J:200070 )

• endothelial cell proliferation is reduced

vision/eye

abnormal retina vasculature morphology ( J:200070 )

• mice treated with tamoxifen at P1-4 show reduced vascular branching in retinal vessels at P5

• mice treated with tamoxifen at P1-4 show fewer distal sprouts with filopodia and fewer number of filopodia in the retinal vasculature

• distal sprouts have fewer side connections in the retinal vasculature of mice treated with tamoxifen at P1-4

• the radial expansion of the vascular plexus is reduced in mice treated with tamoxifen at P1-4

• vessel regression in the retina is increased in tamoxifen treated mice

Genotype
MGI:5792803

cn9

• Allelic Composition: Sox17^tm2Sjm/Sox17^tm2Sjm; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system

abnormal artery morphology ( J:234137 )

• under prolonged angiotensin II (AT II) infusion, tamoxifen treated mice show luminal dilation, wall thinning, and decreased vascular smooth muscle layers at multiple vascular locations around the distal intracerebral bifurcation of intracerebral arteries

• under AT II infusion, endothelial junctions of intracerebral arteries from tamoxifen treated mice are severely disrupted

• under AT II infusion, intracerebral arteries from tamoxifen treated mice show infrequent focal endothelial denudation

abnormal abdominal aorta morphology ( J:234137 )

• under moderate AT II infusion, abdominal aorta of tamoxifen treated mice shows a modest decrease in wall thickness but does not show luminal dilation

abnormal thoracic aorta morphology ( J:234137 )

• under moderate AT II infusion, thoracic aorta of tamoxifen treated mice shows a modest decrease in wall thickness but does not show luminal dilation

aortic dissection ( J:234137 )

• tamoxifen treated mice under AT II infusion occasionally exhibit arterial dissection on the walls of intracranial arteries

abnormal blood vessel endothelium morphology ( J:234137 )

• under AT II infusion, endothelial layers in vessels of tamoxifen treated mice exhibit an abnormal lateral morphology with an irregular and flattened shape

abnormal vascular smooth muscle morphology ( J:234137 )

• arteries from tamoxifen treated mice have less coverage by vascular smooth muscle cells

aneurysm ( J:234137 )

• about 25% of tamoxifen treated mice show abnormally enlarged structure with tortuosity resembling fusiform dilation or a balloon-like structure indicative of saccular aneurysm

• 60% of tamoxifen treated mice subjected to a moderate hypertensive condition by infusion with a low dose of angiotensin II (AT II) exhibit features of intracranial aneurysm, showing vascular enlargement of intracerebral arteries, luminal dilation, and wall thinning

hemorrhage ( J:234137 )

• tamoxifen treated mice under AT II infusion frequently exhibit hemorrhage in cerebrospinal fluid, in the intracranial region, and in the intramural region

• hemorrhage is infrequently seen in mutants under steady state conditions

increased vascular permeability ( J:234137 )

• under AT II infusion, intracerebral arteries from tamoxifen treated mice show increased stress-induced leakage of intravenously infused Evans blue dye

cellular

decreased endothelial cell proliferation ( J:234137 )

• AT II-induced endothelial proliferation is suppressed in the vessels of tamoxifen treated mice

muscle

abnormal vascular smooth muscle morphology ( J:234137 )

• arteries from tamoxifen treated mice have less coverage by vascular smooth muscle cells

Genotype
MGI:5696330

cn10

• Allelic Composition: Gipc1^tm1.1Mhsi/Gipc1^tm1.1Mhsi; Tg(Cdh5-cre/ERT2)1Rha/?
• Genetic Background: involves: 129S1/SvImJ * 129S4/SvJaeSor * C57BL/6

cardiovascular system

abnormal systemic artery morphology ( J:221554 )

• reduced number of collateral arteries

• reduced diameter of input arterioles in the spinotrapezius

abnormal blood circulation ( J:221554 )

• significant decline in blood flow recovery after hind limb ischemia

Genotype
MGI:7435431

cn11

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tg(Cdh5-cre/ERT2)1Rha/0; Gt(ROSA)26Sor^{tm14(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6NCrl * FVB

mortality/aging

postnatal lethality ( J:312482 )

• mice administered tamoxifen at P1 show early lethality beginning at P12

cardiovascular system

cardiovascular system phenotype ( J:312482 )

N • mice administered tamoxifen at P1fail to show frequent cranial hemorrhage or cortical brain arteriovenous malformations (bAVMs) at P14 or P21

Genotype
MGI:7435429

cn12

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S4/SvJae * FVB

mortality/aging

postnatal lethality, incomplete penetrance ( J:312482 )

• mice administered tamoxifen at P1 show lethality beginning at P12

• lethality is not due to failure to thrive

• however, mice treated with tamoxifen between 2 and 4 months of age show no effect on overall survival up to 8 weeks later and show no differences in viability up to 36 weeks later

cardiovascular system

abnormal brain vasculature morphology ( J:312482 )

• mice treated with tamoxifen at P1 show thin and fragile appearing cerebral vessels

• however, vessel density within the brain at P21 is normal

arteriovenous malformation ( J:312482 )

• more than 50% of mice treated with tamoxifen between 2 and 4 months develop brain arteriovenous malformations within 8 weeks of treatment

• however, mice treated with tamoxifen at P1 do not exhibit cortical brain arteriovenous malformations and cerebral vessels do not appear dilated

intracranial hemorrhage ( J:312482 )

• mice administered tamoxifen at P1 that survive to P21 show an incompletely penetrant (11 of 32 mice) phenotype of focal intracranial hemorrhage

• however, mice treated with tamoxifen at P1 do not show hemorrhage in the intestines, lung, or liver at P14

• however, mice treated with tamoxifen between 2 and 4 months do not show hemorrhage 8 weeks after treatment

nervous system

abnormal brain vasculature morphology ( J:312482 )

• mice treated with tamoxifen at P1 show thin and fragile appearing cerebral vessels

• however, vessel density within the brain at P21 is normal

intracranial hemorrhage ( J:312482 )

• mice administered tamoxifen at P1 that survive to P21 show an incompletely penetrant (11 of 32 mice) phenotype of focal intracranial hemorrhage

• however, mice treated with tamoxifen at P1 do not show hemorrhage in the intestines, lung, or liver at P14

• however, mice treated with tamoxifen between 2 and 4 months do not show hemorrhage 8 weeks after treatment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
arteriovenous malformations of the brain		DOID:0060688	OMIM:108010	J:312482

Genotype
MGI:5445987

cn13

• Allelic Composition: Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺; S1pr1^tm2Rlp/S1pr1^tm2Rlp; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ

cardiovascular system

abnormal aorta morphology ( J:189010 )

• glomeruloid lesions form when tamoxifen is administered throughout pregnancy, although these lesions are less severe than in germ line null mice

abnormal retina vasculature morphology ( J:189010 )

• endothelial hyper-sprouting and retention of mural cell coverage on arteries and veins are detected after tamoxifen treatment

vision/eye

abnormal retina vasculature morphology ( J:189010 )

• endothelial hyper-sprouting and retention of mural cell coverage on arteries and veins are detected after tamoxifen treatment

Genotype
MGI:6279216

cn14

• Allelic Composition: Klf2^tm1Mlkn/Klf2⁺; Krit1^tm1Kwhi/Krit1^tm1Kwhi; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl

cardiovascular system

abnormal brain vasculature morphology ( J:232707 )

• tamoxifen injected mice exhibit a marked (80%) but incomplete prevention of cerebral cavernous malformation lesion formation

nervous system

abnormal brain vasculature morphology ( J:232707 )

• tamoxifen injected mice exhibit a marked (80%) but incomplete prevention of cerebral cavernous malformation lesion formation

Genotype
MGI:6279211

cn15

• Allelic Composition: Krit1^tm1Kwhi/Krit1^tm1Kwhi; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl

mortality/aging

premature death ( J:232707 )

• almost all tamoxifen injected mice are dead by P30

cardiovascular system

abnormal brain vasculature morphology ( J:232707 , J:250906 )

• vascular malformation are first seen at P6 of tamoxifen injected mice as dilated venules in the cerebellar white matter, with numerous mature lesions present by P11 (J:232707)

• mice injected with tamoxifen at P1 exhibit cerebral cavernous malformation lesions by P13 (J:250906)

abnormal venule morphology ( J:232707 )

• tamoxifen injected mice exhibit dilated venules in the cerebellar white matter

nervous system

abnormal brain vasculature morphology ( J:232707 , J:250906 )

• vascular malformation are first seen at P6 of tamoxifen injected mice as dilated venules in the cerebellar white matter, with numerous mature lesions present by P11 (J:232707)

• mice injected with tamoxifen at P1 exhibit cerebral cavernous malformation lesions by P13 (J:250906)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebral cavernous malformation		DOID:0060669	OMIM:PS116860	J:232707 , J:250906

Genotype
MGI:6279217

cn16

• Allelic Composition: Klf2^tm1Mlkn/Klf2^tm1Mlkn; Krit1^tm1Kwhi/Krit1^tm1Kwhi; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl

nervous system

nervous system phenotype ( J:232707 )

N • mice exhibit 99% rescue of cerebral cavernous malformation lesion formation, with only a small amount of venule dilatation visible

Genotype
MGI:6279218

cn17

• Allelic Composition: Klf4^tm1Khk/Klf4⁺; Krit1^tm1Kwhi/Krit1^tm1Kwhi; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl

cardiovascular system

abnormal brain vasculature morphology ( J:232707 )

• tamoxifen injected mice exhibit a marked (75%) but incomplete prevention of cerebral cavernous malformation lesion formation

nervous system

abnormal brain vasculature morphology ( J:232707 )

• tamoxifen injected mice exhibit a marked (75%) but incomplete prevention of cerebral cavernous malformation lesion formation

Genotype
MGI:6279215

cn18

• Allelic Composition: Krit1^tm1Kwhi/Krit1^tm1Kwhi; Map3k3^tm1.1Mlkn/Map3k3⁺; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl * C57BL/6NTac

nervous system

nervous system phenotype ( J:232707 )

N • tamoxifen injected mice show a reduction in the number and size of vascular lesions in the brain at P11, with nearly complete prevention of lesions

Genotype
MGI:6361104

cn19

• Allelic Composition: Nus1^tm1Wcsa/Nus1⁺; Rtn4^tm1Matl/Rtn4^tm1Matl; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S7/SvEvBrd

cardiovascular system

cardiovascular system phenotype ( J:230506 )

N • embryos from tamoxifen-treated pregnant females at E8.5 do not show vascular defects

Genotype
MGI:7447283

cn20

• Allelic Composition: Mef2a^tm1.1Limm/Mef2a^tm1.1Limm; Mef2c^tm1Jjs/Mef2c^tm1Jjs; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129S/SvEv * 129S6/SvEvTac

cardiovascular system

abnormal retina vasculature morphology ( J:334208 )

• reduced sprouting angiogenesis in retina at age P5 (4 days after endothelial-cell-specific KO induction): reduced vascular density and coverage in vascular plexus and reduced number of tip cells at angiogenic front

decreased angiogenesis ( J:334208 )

• reduced sprouting angiogenesis in retina at age P5 (4 days after endothelial-cell-specific KO induction): reduced vascular density and coverage in vascular plexus and reduced number of tip cells at angiogenic front

vision/eye

abnormal retina vasculature morphology ( J:334208 )

• reduced sprouting angiogenesis in retina at age P5 (4 days after endothelial-cell-specific KO induction): reduced vascular density and coverage in vascular plexus and reduced number of tip cells at angiogenic front

Genotype
MGI:6723729

cn21

• Allelic Composition: Amotl1^tm1Laho/Amotl1^tm1Laho; Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6

cardiovascular system

abnormal retina vasculature morphology ( J:253854 )

• pups injected with tamoxifen at P1-P3 show a decreased density of the vessel network covering a smaller area of the retina at P6; the vascular density and number of branching points are significantly lower in the periphery and center of P6 retinas

• however, mice injected with tamoxifen at an adult stage show no alterations in the number of branching points and vascular density in adult retinas

abnormal retina blood vessel morphology ( J:253854 )

• pups injected with tamoxifen at P1-P3 show a small but significant reduction in the number of tip cells per vessel length and abnormal pericyte morphology resulting in decreased pericyte coverage of blood vessels in P6 retinas

• however, the number of filopodia per tip cell is relatively normal at P6

abnormal pericyte morphology ( J:253854 )

• pups injected with tamoxifen at P1-P3 show abnormal pericyte morphology, with mural cells "bulging out" from blood vessels, in P6 retinas

vision/eye

abnormal retina vasculature morphology ( J:253854 )

• pups injected with tamoxifen at P1-P3 show a decreased density of the vessel network covering a smaller area of the retina at P6; the vascular density and number of branching points are significantly lower in the periphery and center of P6 retinas

• however, mice injected with tamoxifen at an adult stage show no alterations in the number of branching points and vascular density in adult retinas

abnormal retina blood vessel morphology ( J:253854 )

• pups injected with tamoxifen at P1-P3 show a small but significant reduction in the number of tip cells per vessel length and abnormal pericyte morphology resulting in decreased pericyte coverage of blood vessels in P6 retinas

• however, the number of filopodia per tip cell is relatively normal at P6

Genotype
MGI:6121065

cn22

• Allelic Composition: Amotl2^tm1.1Laho/Amotl2^tm1.1Laho; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6

cardiovascular system

cardiovascular system phenotype ( J:226656 )

N • postnatal retinal angiogenesis

abnormal aorta morphology ( J:226656 )

• embryo aortic endothelial cells shaped short and rounded

aorta stenosis ( J:226656 )

• in 80% of E9.5 embryos

abnormal vascular endothelial cell morphology ( J:226656 )

• embryo aortic endothelial cells shaped short and rounded

• endothelium of embryo posterior cardinal vein (PCV), intersegmental vessels (ISVs) and brain vascular plexus

Genotype
MGI:6514412

cn23

• Allelic Composition: Lypla1^tm1Sem/Lypla1^tm1Sem; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6

cardiovascular system

abnormal physiological neovascularization ( J:302677 )

• mice treated with tamoxifen show decreased hindlimb perfusion recovery after femoral artery ligation (model of peripheral artery disease), with reduced arterial expansion indication decreased arteriogenesis

• tamoxifen-treated mice subjected to femoral artery ligation show decreased pericyte coverage of microvascular networks and decreased numbers of both capillaries and pericytes, indicating decreased angiogenesis

• 2 weeks after femoral artery ligation, fibronectin is increased in the intima, but not the media, of lower extremity arteries compared to controls

Genotype
MGI:6723732

cn24

• Allelic Composition: Amotl1^tm1Laho/Amotl1^tm1Laho; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6

cardiovascular system

abnormal tumor vascularization ( J:253854 )

• tamoxifen-treated mice transplanted with Lewis Lung carcinoma (LLC) cells exhibit a significant increase in tumor blood vessel diameter relative to control mice

• however, tumor weight of LLC tumors is not significantly altered

neoplasm

abnormal tumor vascularization ( J:253854 )

• tamoxifen-treated mice transplanted with Lewis Lung carcinoma (LLC) cells exhibit a significant increase in tumor blood vessel diameter relative to control mice

• however, tumor weight of LLC tumors is not significantly altered

Genotype
MGI:5297596

cn25

• Allelic Composition: Pdcd10^tm1Arte/Pdcd10^tm1Arte; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6

cardiovascular system

abnormal brain vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation lesions within the cerebellum

abnormal retina vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation lesions within the periphery of the retina

nervous system

abnormal brain vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation lesions within the cerebellum

vision/eye

abnormal retina vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation lesions within the periphery of the retina

Genotype
MGI:5297595

cn26

• Allelic Composition: Krit1^tm1Arte/Krit1^tm1Arte; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6

cardiovascular system

abnormal brain vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation lesions within the cerebellum

abnormal retina vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation lesions within the periphery of the retina

nervous system

abnormal brain vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation lesions within the cerebellum

vision/eye

abnormal retina vasculature morphology ( J:177584 )

• mice injected with tamoxifen at P1 develop cerebral cavernous malformation lesions within the periphery of the retina

Genotype
MGI:6121066

cn27

• Allelic Composition: Amotl2^tm1.1Laho/Amotl2⁺; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6

cardiovascular system

abnormal aorta morphology ( J:226656 )

• embryo aortic endothelial cells shaped short and rounded

aorta stenosis ( J:226656 )

• in 80% of E9.5 embryos

abnormal vascular endothelial cell morphology ( J:226656 )

• embryo aortic endothelial cells shaped short and rounded

Genotype
MGI:5608673

cn28

• Allelic Composition: Rhoj^tm1.1Auem/Rhoj^tm1.1Auem; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6 * CBA/JNCrlj

neoplasm

abnormal tumor vascularization ( J:208154 )

• decrease in vascular densities in peri- and intratumoral areas, decreased pericyte and basement membrane coverage and increased vascular permeability in tumors formed by injection of Lewis lung carcinoma cells

abnormal tumor morphology ( J:208154 )

• tumors formed by injection of Lewis lung carcinoma cells show an increase in hemorrhagic necrosis

decreased tumor growth/size ( J:208154 )

• decreased growth of injected Lewis lung carcinoma cells

• decrease in growth is less than in mice with a germ line deletion of Rhoj

cardiovascular system

abnormal tumor vascularization ( J:208154 )

• decrease in vascular densities in peri- and intratumoral areas, decreased pericyte and basement membrane coverage and increased vascular permeability in tumors formed by injection of Lewis lung carcinoma cells

internal hemorrhage ( J:208154 )

• tumors formed by injection of Lewis lung carcinoma cells show an increase in hemorrhagic foci

Genotype
MGI:6723730

cn29

• Allelic Composition: Amotl1^tm1Laho/Amotl1^tm1Laho; Tg(Cdh5-cre/ERT2)1Rha/0; Tg(MMTV-PyVT)634Mul/0
• Genetic Background: involves: C57BL/6 * FVB/N

cardiovascular system

abnormal tumor vascularization ( J:253854 )

• mice injected with tamoxifen show significantly enlarged and dilated infiltrating blood vessels in the mammary tumor area relative to control mice, as determined by vessel diameter

• however, adult retinal vessels from these mice exhibit no changes in vessel diameter

neoplasm

abnormal tumor vascularization ( J:253854 )

• mice injected with tamoxifen show significantly enlarged and dilated infiltrating blood vessels in the mammary tumor area relative to control mice, as determined by vessel diameter

• however, adult retinal vessels from these mice exhibit no changes in vessel diameter

increased tumor latency ( J:253854 )

• mice injected with tamoxifen exhibit a longer lag time until mammary gland tumors are detected relative to control mice

• however, overall tumor progression is not affected

Genotype
MGI:6415692

cn30

• Allelic Composition: Flvcr2^tm1.1Tda/Flvcr2^tm1.2Tda; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6J

cardiovascular system

cardiovascular system phenotype ( J:287134 )

N • tamoxifen-treated mice exhibit normal blood brain barrier function

Genotype
MGI:6415689

cn31

• Allelic Composition: Flvcr2^tm1.1Tda/Flvcr2^tm1.1Tda; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6J

cardiovascular system

cardiovascular system phenotype ( J:287134 )

N • tamoxifen-treated mice exhibit normal blood brain barrier function

abnormal vascular endothelial cell morphology ( J:287134 )

• in response to supra-physiologic levels of VEGF, endothelial cells from tamoxifen-treated embryos exhibit reduced ability to adopt a tip cell phenotype compared with control cells

cellular

decreased endothelial cell proliferation ( J:287134 )

• in cells from tamoxifen-treated embryos in response to supra-physiologic levels of VEGF

Genotype
MGI:6364849

cn32

• Allelic Composition: Sdc2^{tm1c(KOMP)Wtsi}/Sdc2^{tm1c(KOMP)Wtsi}; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6J * C57BL/6N

cardiovascular system

decreased angiogenesis ( J:276769 )

• induced by VEGFA165 in retinal from tamoxifen-treated mice in a cornea pocket assay model

• however, response to FGF2 is normal

homeostasis/metabolism

decreased susceptibility to injury ( J:276769 )

• reduced blood flow after common femoral artery ligation with reduced perfused arterial vessels and vessel size in tamoxifen-treated mice

Genotype
MGI:7596537

cn33

• Allelic Composition: Cyb5r1^{tm1c(KOMP)Wtsi}/Cyb5r1^{tm1c(KOMP)Wtsi}; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6N

mortality/aging

prenatal lethality ( J:344225 )

• pups were dead on inspection post-delivery from unknown cause

Genotype
MGI:5470092

cn34

• Allelic Composition: Pfn1^tm1Foxp/Pfn1^tm1Foxp; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: involves: C57BL/6NTac

cardiovascular system

decreased angiogenesis ( J:193938 )

• after ischemia, tamoxifen-treated mice exhibit impaired angiogenesis and reduced perfusion compared with control mice

Genotype
MGI:5445989

cn35

• Allelic Composition: Cdh5^tm1Dvst/Cdh5^tm1Dvst; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: Not Specified

cardiovascular system

abnormal retina vasculature morphology ( J:189010 )

• prominent endothelial hyper-sprouting

• detaching tip cells have poor cellular connections to the vascular plexus at the angiogenic front and show signs of increased motility

vision/eye

abnormal retina vasculature morphology ( J:189010 )

• prominent endothelial hyper-sprouting

• detaching tip cells have poor cellular connections to the vascular plexus at the angiogenic front and show signs of increased motility

Genotype
MGI:5771679

cn36

• Allelic Composition: Cpt1a^tm1.1Pec/Cpt1a^tm1.1Pec; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: Not Specified

cardiovascular system

abnormal retina vasculature morphology ( J:220527 )

• mice injected with tamoxifen at P1-P4 exhibit a reduced number of vascular branch points and reduced radial expansion of the vascular plexus at P5, as shown by isolectin-B4 staining of retinal vessels

• vascular sprouting defects are due to impaired endothelial cell proliferation

• no increase in retinal vessel regression or changes in filopodia number or vessel maturation are observed

decreased vascular endothelial cell proliferation ( J:220527 )

• mice injected with tamoxifen at P1-P4 exhibit reduced endothelial cell proliferation in retinal vessels at P5, as shown by EdU staining

cellular

decreased vascular endothelial cell proliferation ( J:220527 )

• mice injected with tamoxifen at P1-P4 exhibit reduced endothelial cell proliferation in retinal vessels at P5, as shown by EdU staining

vision/eye

abnormal retina vasculature morphology ( J:220527 )

• mice injected with tamoxifen at P1-P4 exhibit a reduced number of vascular branch points and reduced radial expansion of the vascular plexus at P5, as shown by isolectin-B4 staining of retinal vessels

• vascular sprouting defects are due to impaired endothelial cell proliferation

• no increase in retinal vessel regression or changes in filopodia number or vessel maturation are observed

Genotype
MGI:6361095

cn37

• Allelic Composition: Nus1^tm1Wcsa/Nus1^tm1Wcsa; Tg(Cdh5-cre/ERT2)1Rha/0
• Genetic Background: Not Specified

mortality/aging

embryonic lethality, complete penetrance ( J:230506 )

• embryos from tamoxifen-treated females at E8.5 and E9.5 die 5 days after tamoxifen injection

embryo

abnormal vitelline vasculature morphology ( J:230506 )

• yolk sacs show vascular defects in embryos from tamoxifen-treated females at E8.5 and E9.5

abnormal jugular lymph sac morphology ( J:230506 )

• embryos from tamoxifen-treated females at E8.5 and E9.5 show blood filled jugular lymph sacs at E13.5

cardiovascular system

abnormal vascular development ( J:230506 )

• embryos from tamoxifen-treated females at E8.5 and E9.5 show dilation of subcutaneous microvessels and blood filled jugular lymph sacs at E13.

• reduction in vascular density and disorganized vascular networks are seen in embryonic tissues (hindbrain, skin, and hindlimb) of embryos from tamoxifen-treated females at E8.5 and E9.5

abnormal vitelline vasculature morphology ( J:230506 )

• yolk sacs show vascular defects in embryos from tamoxifen-treated females at E8.5 and E9.5

hemorrhage ( J:230506 )

• embryos from tamoxifen-treated females at E8.5 and E9.5 exhibit extensive multifocal subcutaneous hemorrhages at E12.5 and E13.5

increased vascular endothelial cell apoptosis ( J:230506 )

• dorsal skin of embryos from tamoxifen-treated females show increased apoptosis

cellular

increased vascular endothelial cell apoptosis ( J:230506 )

• dorsal skin of embryos from tamoxifen-treated females show increased apoptosis

decreased endothelial cell proliferation ( J:230506 )

• embryos from tamoxifen-treated females at E8.5 and E9.5 show 48% reductions in endothelial cell proliferation at E12.5

homeostasis/metabolism

subcutaneous edema ( J:230506 )

• embryos from tamoxifen-treated females at E8.5 and E9.5 exhibit subcutaneous edema

immune system

abnormal jugular lymph sac morphology ( J:230506 )

• embryos from tamoxifen-treated females at E8.5 and E9.5 show blood filled jugular lymph sacs at E13.5

integument

subcutaneous edema ( J:230506 )

• embryos from tamoxifen-treated females at E8.5 and E9.5 exhibit subcutaneous edema