Phenotypes associated with this allele

• Allele Symbol: Dll4⁺
• Allele Name: wild type
• Allele ID: MGI:2439201
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Dll4^tm1Grid/Dll4^+	either: (involves: 129X1/SvJ * Black Swiss) or (involves: 129X1/SvJ * C57BL/6J)	MGI:3056463
ht2	Dll4^tm1Jrt/Dll4^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3056439
ht3	Dll4^tm1Jrt/Dll4^+	involves: 129S1/Sv * 129X1/SvJ * ICR	MGI:3056438
ht4	Dll4^tm1Nwg/Dll4^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac	MGI:3522504
ht5	Dll4^tm1Nwg/Dll4^+	involves: 129S6/SvEvTac * C57BL/6NTac * ICR	MGI:3522506
cn6	Dll4^tm2.1Vlcg/Dll4^+ Gt(ROSA)26Sor^tm2(cre/ERT2)Brn/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6NTac	MGI:5302388
cn7	Dll4^tm1Frad/Dll4^+ Isl1^tm1(cre)Tmj/Isl1^+	involves: 129S1/Sv * 129X1/SvJ	MGI:7545577
cn8	Dll4^tm3.1Vlcg/Dll4^+ Gt(ROSA)26Sor^tm3.1(cre/ERT2)Vlcg/Gt(ROSA)26Sor^+	involves: 129S6/SvEvTac * C57BL/6NTac	MGI:5546218
cn9	Dll4^tm2.1Vlcg/Dll4^+ Tg(Nanog-cre)#Vlcg/0	involves: 129S6/SvEvTac * C57BL/6NTac	MGI:5546216

Genotype
MGI:3056463

ht1

• Allelic Composition: Dll4^tm1Grid/Dll4⁺
• Genetic Background: either: (involves: 129X1/SvJ * Black Swiss) or (involves: 129X1/SvJ * C57BL/6J)

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

mortality/aging

preweaning lethality, complete penetrance ( J:93125 )

• only a single heterozygote was produced and no heterozygous pups were produced from mating this individual to wild-type Black Swiss females

cardiovascular system

abnormal dorsal aorta morphology ( J:93125 )

• some embryos also have more caudal fusions of the dorsal aorta to the common cardinal vein

abnormal capillary morphology ( J:93125 )

• the capillary system is less extensive and more primitive compared to wild-type

abnormal vascular regression ( J:93125 )

• no vascular remodeling is seen at E9.5

abnormal anterior cardinal vein morphology ( J:93125 )

• the distal outflow tract is connected to the anterior cardinal vein by an anastamoses

abnormal common cardinal vein morphology ( J:93125 )

• some embryos also have more caudal fusions of the dorsal aorta to the common cardinal vein

arteriovenous malformation ( J:93125 )

• the distal outflow tract is connected to the anterior cardinal vein by an anastamoses

• some embryos also have more caudal fusions of the dorsal aorta to the common cardinal vein

blood vessel atresia ( J:93125 )

• some vessels are reduced in diameter or atretic

pericardial effusion ( J:93125 )

• pericardial effusion is seen at E9.5 and E10.5

embryo

embryonic growth retardation ( J:93125 )

• embryonic growth retardation is seen at E9.5 and E10.5

abnormal vitelline vascular remodeling ( J:93125 )

• a mottled avascular yolk sac is seen at E9.5 and E10.5

• the yolk sac primary plexus is not remodeled

growth/size/body

embryonic growth retardation ( J:93125 )

• embryonic growth retardation is seen at E9.5 and E10.5

homeostasis/metabolism

pericardial effusion ( J:93125 )

• pericardial effusion is seen at E9.5 and E10.5

cellular

abnormal vascular regression ( J:93125 )

• no vascular remodeling is seen at E9.5

Genotype
MGI:3056439

ht2

• Allelic Composition: Dll4^tm1Jrt/Dll4⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:93157 )

• total embryonic lethality is seen after E10.5 when chimeras are crossed to 129S1/Sv females

Genotype
MGI:3056438

ht3

• Allelic Composition: Dll4^tm1Jrt/Dll4⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * ICR

mortality/aging

prenatal lethality, incomplete penetrance ( J:93157 )

• partial lethality is seen after E10.5 when chimeras are crossed to ICR females

cardiovascular system

abnormal dorsal aorta morphology ( J:93157 )

• the diameter of the dorsal aorta is reduced in 60% of embryos at E9.0 and in 90% of embryos at E9.5 and E10.5

• the location and extent of constriction varied, but was primarily observed rostrally between the cardiac level and the intersections with the branchial arch arteries, but some embryos exhibited longer zones of constriction extending caudally

abnormal umbilical artery morphology ( J:93157 )

• the umbilical artery is reduced in size

abnormal placenta vasculature ( J:93157 )

• the placental blood vessels are reduced in size

abnormal cardinal vein morphology ( J:93157 )

• the anterior and posterior cardinal veins were reduced in caliber and disorganized in embryos with severely constricted dorsal aortas

abnormal vitelline vasculature morphology ( J:93157 )

• the major vitelline arteries and arterial branching on the yolk sac are reduced in all embryos

abnormal pericardial cavity morphology ( J:93157 )

• the pericardial space is enlarged in more severely affected embryos at E10.5

poor circulation ( J:93157 )

• all embryos show reduced vitelline circulation

embryo

abnormal umbilical artery morphology ( J:93157 )

• the umbilical artery is reduced in size

abnormal placenta vasculature ( J:93157 )

• the placental blood vessels are reduced in size

abnormal vitelline vasculature morphology ( J:93157 )

• the major vitelline arteries and arterial branching on the yolk sac are reduced in all embryos

embryonic growth retardation ( J:93157 )

• a progressive developmental delay is seen in some embryos starting at E8.5

growth/size/body

embryonic growth retardation ( J:93157 )

• a progressive developmental delay is seen in some embryos starting at E8.5

Genotype
MGI:3522504

ht4

• Allelic Composition: Dll4^tm1Nwg/Dll4⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:94740 )

• almost all heterozygous embryos die around E10.5 with only 2.4% appearing viable, however these can survive to adulthood

• Background Sensitivity: when outbred onto an ICR background survival increases

cardiovascular system

abnormal blood vessel morphology ( J:94740 )

aorta stenosis ( J:94740 )

• the aorta is variably stenosed or atretic along its length

abnormal internal carotid artery morphology ( J:94740 )

• the internal carotid artery is absent

abnormal induced retina neovascularization ( J:177797 )

• retinal capillaries are more resistant to oxygen-induced vaso-obliteration compared with wild-type capillaries

abnormal placenta vasculature ( J:94740 )

• the major placental arteries appear to degenerate leaving only atretic remnants

abnormal vascular development ( J:94740 )

abnormal artery development ( J:94740 )

• a defined arterial plexus is missing resulting in the absence of many of the well defined arterial branches, including the internal carotid artery

abnormal dorsal aorta morphology ( J:94740 )

• in places the dorsal aortas lack lumens and appear to be comprised of only nonorganized endothelial cell clusters

abnormal vascular regression ( J:94740 )

• remodeling of the primitive vascular plexus of the head is impaired resulting in absence of a defined arterial plexus however in most cases the venous plexus was relatively normal

abnormal vein development ( J:94740 )

• in the most severely affected embryos the primitive venous plexus does not properly coalesce

abnormal cardinal vein morphology ( J:94740 )

• in severely affected embryos the anterior and posterior cardinal veins are variably stenosed or atretic

absent vitelline blood vessels ( J:94740 )

• the large conducting arteries and collecting veins within the yolk sac are absent

• the endothelium forms an almost continuous surface punctuated with occasional holes

abnormal vascular smooth muscle morphology ( J:94740 )

• smooth muscle coverage of many of the large arteries is missing or reduced

embryo

abnormal placenta vasculature ( J:94740 )

• the major placental arteries appear to degenerate leaving only atretic remnants

absent vitelline blood vessels ( J:94740 )

• the large conducting arteries and collecting veins within the yolk sac are absent

• the endothelium forms an almost continuous surface punctuated with occasional holes

embryo tissue necrosis ( J:94740 )

• the posterior half of the embryo is frequently necrotic at E9.5-E10.5

abnormal visceral yolk sac morphology ( J:94740 )

• the yolk sac has an orange peel like texture and an enlarged endothelial-lined lacunae forms between the endodermal and mesodermal layers resulting in decreased attachment of these layers

muscle

abnormal vascular smooth muscle morphology ( J:94740 )

• smooth muscle coverage of many of the large arteries is missing or reduced

vision/eye

abnormal induced retina neovascularization ( J:177797 )

• retinal capillaries are more resistant to oxygen-induced vaso-obliteration compared with wild-type capillaries

cellular

abnormal vascular regression ( J:94740 )

• remodeling of the primitive vascular plexus of the head is impaired resulting in absence of a defined arterial plexus however in most cases the venous plexus was relatively normal

Genotype
MGI:3522506

ht5

• Allelic Composition: Dll4^tm1Nwg/Dll4⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NTac * ICR

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:94740 )

• over half of all heterozygous embryos die around E10.5

• Background Sensitivity: survival is increased compared to heterozygotes on a mixed 129, C57BL/6 background

Genotype
MGI:5302388

cn6

• Allelic Composition: Dll4^tm2.1Vlcg/Dll4⁺; Gt(ROSA)26Sor^{tm2(cre/ERT2)Brn}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6NTac

cardiovascular system

abnormal induced retina neovascularization ( J:177797 )

• retinal capillaries from tamoxifen-treated mice are more resistant to oxygen-induced vaso-obliteration compared with control capillaries

abnormal vascular regression ( J:177797 )

• tamoxifen-treated mice exhibit reduced capillary regression during normal developmental capillary remodeling compared with control mice

vision/eye

abnormal induced retina neovascularization ( J:177797 )

• retinal capillaries from tamoxifen-treated mice are more resistant to oxygen-induced vaso-obliteration compared with control capillaries

cellular

abnormal vascular regression ( J:177797 )

• tamoxifen-treated mice exhibit reduced capillary regression during normal developmental capillary remodeling compared with control mice

Genotype
MGI:7545577

cn7

• Allelic Composition: Dll4^tm1Frad/Dll4⁺; Isl1^tm1(cre)Tmj/Isl1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

cardiovascular system

abnormal cardiac outflow tract development ( J:308916 )

• 9 of 28 embryos show outflow tract alignment defects

• however, septation of the outflow tract is preserved

double outlet right ventricle ( J:308916 )

• in embryos with a severe ventricular septal defect

overriding aortic valve ( J:308916 )

• in embryos with a shallower ventricular septal defect

ventricular septal defect ( J:308916 )

• some embryos show a prominent ventricular septal defect while in others this is more shallow

abnormal pulmonary valve morphology ( J:308916 )

• pulmonary valve arises more cranially and exits the right ventricle

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Adams-Oliver syndrome		DOID:0060227	OMIM:100300 OMIM:614219 OMIM:614814 OMIM:615297 OMIM:616028 OMIM:PS100300	J:308916

Genotype
MGI:5546218

cn8

• Allelic Composition: Dll4^tm3.1Vlcg/Dll4⁺; Gt(ROSA)26Sor^{tm3.1(cre/ERT2)Vlcg}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NTac

normal phenotype

no abnormal phenotype detected ( J:200671 )

Genotype
MGI:5546216

cn9

• Allelic Composition: Dll4^tm2.1Vlcg/Dll4⁺; Tg(Nanog-cre)#Vlcg/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NTac

cardiovascular system

abnormal angiogenesis ( J:200671 )

• severe as in Dll4^tm1Nwg heterozygotes

embryo

abnormal embryo development ( J:200671 )

• authors state that mice phenocopy Dll4^tm1Nwg heterozygotes