Phenotypes associated with this allele

• Allele Symbol: Vegfa^tm2Gne
• Allele Name: targeted mutation 2, Genentech
• Allele ID: MGI:1931048
• Summary: 18 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Vegfa^tm2Gne/Vegfa^+ Tg(Nphs1-cre)1Seq/0	involves: 129	MGI:2654003
cn2	Vegfa^tm2Gne/Vegfa^tm2Gne Tg(Nphs1-cre)1Seq/0	involves: 129	MGI:2654008
cn3	Vegfa^tm2Gne/Vegfa^tm2Gne Tg(Pax6-cre,GFP)2Pgr/0	involves: 129	MGI:5705506
cn4	Vegfa^tm2Gne/Vegfa^+ Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0	involves: 129 * C57BL/6	MGI:4938194
cn5	Vegfa^tm2Gne/Vegfa^tm2Gne Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0	involves: 129 * C57BL/6	MGI:4938179
cn6	Vegfa^tm2Gne/Vegfa^tm2Gne Lyz2^tm1(cre)Ifo/Lyz2^+ Tg(KRT14-cre)1Cgn/0	involves: 129 * C57BL/6 * CBA * FVB/N	MGI:5444295
cn7	Vegfa^tm2Gne/Vegfa^tm2Gne Tg(Csf1r-cre/Esr1*)1Jwp/0	involves: 129 * C57BL/6 * FVB/N	MGI:5435892
cn8	Kdr^tm2Sato/Kdr^tm2Sato Vegfa^tm2Gne/Vegfa^tm2Gne Tg(Pax6-cre,GFP)2Pgr/0	involves: 129S1/Sv	MGI:5705505
cn9	Vegfa^tm2Gne/Vegfa^tm2.1Nagy Tg(Nes-cre)1Kln/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL	MGI:4422207
cn10	Vegfa^tm2Gne/Vegfa^+ Tg(Nes-cre)1Kln/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL	MGI:4422199
cn11	Vegfa^tm2Gne/Vegfa^tm2Gne Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129/Sv * 129P2/OlaHsd	MGI:4418463
cn12	Vegfa^tm2Gne/Vegfa^tm2Gne Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129/Sv * 129P2/OlaHsd * C57BL/6	MGI:4418501
cn13	Vegfa^tm2Gne/Vegfa^tm2Gne Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129/Sv * 129P2/OlaHsd * FVB/N	MGI:5444293
cn14	Vegfa^tm2Gne/Vegfa^tm2Gne E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129/Sv * C3H * C57BL/6	MGI:7343722
cn15	Vegfa^tm2Gne/Vegfa^tm2Gne Tg(Mx1-cre)1Cgn/0	involves: 129/Sv * C57BL/6 * CBA	MGI:2183820
cn16	Vegfa^tm2Gne/Vegfa^tm2Gne Tg(Tnnt2-cre)5Blh/0	involves: 129/Sv * C57BL/6 * DBA	MGI:5471120
cn17	Vegfa^tm2Gne/Vegfa^tm2Gne Tg(Prrx1-cre)1Cjt/0	involves: 129/Sv * C57BL/6J * SJL/J	MGI:3840960
cn18	Vegfa^tm2Gne/Vegfa^tm2Gne Tg(SFTPC-cre)#Mliu/0	involves: 129/Sv * ICR	MGI:4440740

Genotype
MGI:2654003

cn1

• Allelic Composition: Vegfa^tm2Gne/Vegfa⁺; Tg(Nphs1-cre)1Seq/0
• Genetic Background: involves: 129

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

behavior/neurological

lethargy ( J:82440 )

• mutants are lethargic at 9-12 weeks of age

hematopoietic system

anemia ( J:82440 )

• normochromic, normocytic anemia

homeostasis/metabolism

increased circulating creatinine level ( J:82440 )

• more than 10 times the nomral levels of creatinine

increased blood urea nitrogen level ( J:82440 )

• elevation in urea

increased urine protein level ( J:82440 )

albuminuria ( J:82440 )

renal/urinary system

increased urine protein level ( J:82440 )

albuminuria ( J:82440 )

abnormal kidney morphology ( J:82440 )

• renal lesions are first detected at 2.5 weeks of age with swelling of the endothelial cells and hyaline deposits

abnormal glomerular capillary morphology ( J:82440 )

• no patent capillary loops can be seen at 9 weeks of age

abnormal glomerular capillary endothelium morphology ( J:82440 )

• at 2.5 weeks of age, mice display swelling of the endothelial cells (endotheliosis)

• endothelial cells become necrotic by 9 weeks of age

absent glomerular endothelium fenestra ( J:82440 )

• endothelial fenestrations are no longer identifiable by 9 weeks of age

• however, well-formed endothelial fenestrations are present at 2.5 weeks of age

abnormal podocyte morphology ( J:82440 )

• podocytes containing large empty cytoplasmic vacuoles are seen by 9 weeks of age

podocyte foot process effacement ( J:82440 )

• no podocyte foot processes are identifiable by 9 weeks of age

increased renal glomerulus basement membrane thickness ( J:82440 )

• at 6.5 weeks of age, the glomerular basement membrane is expanded

expanded mesangial matrix ( J:82440 )

• expansion of the mesangial matrix is seen by 9 weeks of age

glomerulosclerosis ( J:82440 )

• hyaline deposits are first detected at 2.5 weeks of age

kidney atrophy ( J:82440 )

• pale, shrunken kidneys at 9 weeks of age

renal glomerulus atrophy ( J:82440 )

• glomerular tufts are retracted by 9 weeks of age

dilated renal tubule ( J:82440 )

• dilated tubules can be seen at 9 weeks of age

renal cast ( J:82440 )

• dilated tubules are packed with proteinaceous material in most places

pale kidney ( J:82440 )

• at 9 weeks of age

kidney failure ( J:82440 )

• develop end-stage kidney failure by 9-12 weeks of age

• no gross signs of renal failure prior to 7-8 weeks of age

integument

decreased skin turgor ( J:82440 )

cardiovascular system

abnormal glomerular capillary morphology ( J:82440 )

• no patent capillary loops can be seen at 9 weeks of age

abnormal glomerular capillary endothelium morphology ( J:82440 )

• at 2.5 weeks of age, mice display swelling of the endothelial cells (endotheliosis)

• endothelial cells become necrotic by 9 weeks of age

absent glomerular endothelium fenestra ( J:82440 )

• endothelial fenestrations are no longer identifiable by 9 weeks of age

• however, well-formed endothelial fenestrations are present at 2.5 weeks of age

Genotype
MGI:2654008

cn2

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Tg(Nphs1-cre)1Seq/0
• Genetic Background: involves: 129

mortality/aging

perinatal lethality, complete penetrance ( J:82440 )

• die at birth or within 18 hours of birth

homeostasis/metabolism

edema ( J:82440 )

• some mice are born with hydrops

renal/urinary system

abnormal podocyte morphology ( J:82440 )

• podocytes are present but pile up in several layers

podocyte foot process effacement ( J:82440 )

• widespread but not complete effacement of podocyte foot processes

abnormal podocyte slit diaphragm morphology ( J:82440 )

• podocytes lack well-formed slit diaphragms

abnormal renal glomerulus morphology ( J:82440 )

• all glomeruli are small, fail to develop fully, and do not form filtration barriers

• no or few glomerular capillary loops are identified

abnormal glomerular capillary morphology ( J:82440 )

• lack of visible capillary loops

abnormal glomerular capillary endothelium morphology ( J:82440 )

• endothelial cells are reduced in number in immature glomeruli while mature glomeruli lack endothelial cells

absent glomerular endothelium fenestra ( J:82440 )

• no fenestrations are observed in endothelial cells

abnormal mesangial cell morphology ( J:82440 )

• VSMA (a marker for mesangial cells) is absent although some desmin staining is observed, indicating a defect in migration and/or differentiation of mesangial cells into the glomerulus

abnormal glomerular filtration barrier morphology ( J:82440 )

• glomeruli fail to form filtration barriers

cortical renal glomerulopathies ( J:82440 )

cardiovascular system

abnormal glomerular capillary morphology ( J:82440 )

• lack of visible capillary loops

abnormal glomerular capillary endothelium morphology ( J:82440 )

• endothelial cells are reduced in number in immature glomeruli while mature glomeruli lack endothelial cells

absent glomerular endothelium fenestra ( J:82440 )

• no fenestrations are observed in endothelial cells

cellular

abnormal mesangial cell morphology ( J:82440 )

• VSMA (a marker for mesangial cells) is absent although some desmin staining is observed, indicating a defect in migration and/or differentiation of mesangial cells into the glomerulus

Genotype
MGI:5705506

cn3

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Tg(Pax6-cre,GFP)2Pgr/0
• Genetic Background: involves: 129

cardiovascular system

abnormal retina vasculature morphology ( J:217533 )

• some arteriovenous crossings is observed

vision/eye

abnormal retina vasculature morphology ( J:217533 )

• some arteriovenous crossings is observed

Genotype
MGI:4938194

cn4

• Allelic Composition: Vegfa^tm2Gne/Vegfa⁺; Tg(SFTPC-rtTA)5Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * C57BL/6

respiratory system

decreased pulmonary endothelial cell surface ( J:124125 )

• at E18.5, doxycycline-exposed mice exhibit a reduction in pulmonary endothelial cell development that is intermediate between those of wild-type controls and those carrying two Vegfa^tm2Gne alleles

abnormal pulmonary circulation ( J:124125 )

• newborn mice exposed to doxycycline from E6.5 display pale lungs, indicating reduced pulmonary circulation

abnormal lung development ( J:124125 )

• mice exposed to doxycycline from E6.5 display defective distal lung saccular development due to moderately reduced primary septation

abnormal lung saccule morphology ( J:124125 )

• at E18.5, doxycycline-exposed mice display dilated distal airspaces of a size that is intermediate between those of wild-type controls and those carrying two Vegfa^tm2Gne alleles

• the mean linear intercept, a reflection of airspace size and hence an indirect measure of septation incidence, is inversely related to the Vegfa gene dosage

pale lung ( J:124125 )

• newborn mice exposed to doxycycline from E6.5 display pale lungs

cardiovascular system

decreased pulmonary endothelial cell surface ( J:124125 )

• at E18.5, doxycycline-exposed mice exhibit a reduction in pulmonary endothelial cell development that is intermediate between those of wild-type controls and those carrying two Vegfa^tm2Gne alleles

abnormal pulmonary circulation ( J:124125 )

• newborn mice exposed to doxycycline from E6.5 display pale lungs, indicating reduced pulmonary circulation

Genotype
MGI:4938179

cn5

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Tg(SFTPC-rtTA)5Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:124125 )

• newborn mice exposed to doxycycline from E6.5 develop respiratory distress and die within 1-2 hrs of birth

respiratory system

abnormal lung vasculature morphology ( J:124125 )

• at E18.5, doxycycline-exposed mice display an almost complete absence of pulmonary capillaries associated with defective primary septation during distal lung morphogenesis

• at E18.5, lung saccular walls without capillaries exhibit no septae while septae containing a residual (single) capillary or disorganized capillaries are malformed and show abnormal shapes with an expanded mesenchyme

decreased pulmonary endothelial cell surface ( J:124125 )

• at E18.5, doxycycline-exposed mice exhibit significantly reduced pulmonary endothelial cell development relative to controls

abnormal pulmonary circulation ( J:124125 )

• at birth, doxycycline-exposed mice display white lungs, indicating a lack of pulmonary circulation

abnormal lung development ( J:124125 )

• mice exposed to doxycycline from E6.5 display defective distal lung saccular development due to reduced primary septation; first seen at E16.5 when terminal tubules appear more dilated

• defective distal airspace morphogenesis is also noted when mice are exposed to doxycycline from E14.5 to birth

• impaired primary septation is likely due to reduced hepatocyte growth factor (Hgf) expression

decreased mesenchymal cell proliferation involved in lung development ( J:124125 )

• at E18.5, doxycycline-exposed mice display a significant reduction in proliferating (BrdU+) lung mesenchymal cells relative to controls

abnormal lung saccule morphology ( J:124125 )

• at E18.5, doxycycline-exposed mice display significantly dilated distal airspaces with fewer subdivisions by primary septae than controls

• at E18.5, doxycycline-exposed mice display a mosaic pattern of normal and abnormal septae that is dependent on the residual capillary structures

• at birth, ventilation of doxycycline-exposed lungs results in marked dilation of terminal airspaces and thinning of saccular walls

abnormal lung epithelium morphology ( J:124125 )

• at E18.5, doxycycline-exposed mice display a 65% reduction in proliferating (BrdU+) lung epithelial cells relative to controls

• however, epithelial cell survival and proximal-distal patterning of epithelial cell differentiation remain normal

abnormal pulmonary acinus morphology ( J:124125 )

• at E16.5 and E17.5, doxycycline-exposed mice display abnormal distal acini and more dilated distal tubules than controls

pale lung ( J:124125 )

• at birth, doxycycline-exposed mice display white lungs

respiratory distress ( J:124125 )

• newborn mice exposed to doxycycline from E6.5 develop respiratory distress and die within 1-2 hrs of birth

cardiovascular system

abnormal lung vasculature morphology ( J:124125 )

• at E18.5, doxycycline-exposed mice display an almost complete absence of pulmonary capillaries associated with defective primary septation during distal lung morphogenesis

• at E18.5, lung saccular walls without capillaries exhibit no septae while septae containing a residual (single) capillary or disorganized capillaries are malformed and show abnormal shapes with an expanded mesenchyme

decreased pulmonary endothelial cell surface ( J:124125 )

• at E18.5, doxycycline-exposed mice exhibit significantly reduced pulmonary endothelial cell development relative to controls

decreased angiogenesis ( J:124125 )

• at E18.5, doxycycline-exposed mice display significantly reduced pulmonary capillary angiogenesis associated with defective primary septation during distal lung morphogenesis

abnormal pulmonary circulation ( J:124125 )

• at birth, doxycycline-exposed mice display white lungs, indicating a lack of pulmonary circulation

cellular

decreased mesenchymal cell proliferation involved in lung development ( J:124125 )

• at E18.5, doxycycline-exposed mice display a significant reduction in proliferating (BrdU+) lung mesenchymal cells relative to controls

Genotype
MGI:5444295

cn6

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Lyz2^tm1(cre)Ifo/Lyz2⁺; Tg(KRT14-cre)1Cgn/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * FVB/N

homeostasis/metabolism

abnormal wound healing ( J:189044 )

• during the early and middle phases of wound healing, mice exhibit reduced formation and vascularization of granulation tissue compared with control mice

Genotype
MGI:5435892

cn7

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Tg(Csf1r-cre/Esr1*)1Jwp/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

neoplasm

decreased metastatic potential ( J:186831 )

• after tamoxifen-induced recombination to ablate Vegfa in cultured bone marrow-derived macrophages, the BMDMs are unable to promote trans-endothelial migration of tumor cells or enhance permeability of the endothelial monolayer, both important for metastasis

• adoptive transfer of Vegfa-null monocytes infiltrate lung metastases comparably to wild-type inflammatory monocytes

Genotype
MGI:5705505

cn8

• Allelic Composition: Kdr^tm2Sato/Kdr^tm2Sato; Vegfa^tm2Gne/Vegfa^tm2Gne; Tg(Pax6-cre,GFP)2Pgr/0
• Genetic Background: involves: 129S1/Sv

cardiovascular system

abnormal retina vasculature morphology ( J:217533 )

• some arteriovenous crossings is observed

• however, mice do not exhibit early vertical vascular branching in the retina observed in Kdr^tm2.1Jrt/Kdr^tm2.1Jrt Tg(Pax6-cre,GFP)2Pgr mice

vision/eye

abnormal retina vasculature morphology ( J:217533 )

• some arteriovenous crossings is observed

• however, mice do not exhibit early vertical vascular branching in the retina observed in Kdr^tm2.1Jrt/Kdr^tm2.1Jrt Tg(Pax6-cre,GFP)2Pgr mice

Genotype
MGI:4422207

cn9

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2.1Nagy; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:86207 )

• mice die of dehydration within 24 hours of birth

nervous system

abnormal brain vasculature morphology ( J:86207 )

• at P1, the cerebral cortex lacks pial vasculature unlike in wild-type mice

• mice exhibit deficient vascular development in the superficial levels of the cortex near the marginal zone and cortical plate, and in the deep ventricular zone compared with wild-type mice

• mice exhibit defects in blood vessel density compared with wild-type mice

• at P1, mice exhibit a decrease in the number of branch points of blood vessels in the cortex and forebrain while the distance between branch points is increased compared with wild-type mice

hydrocephaly ( J:86207 )

enlarged lateral ventricles ( J:86207 )

• in neonates

abnormal choroid plexus morphology ( J:86207 )

abnormal cerebral cortex morphology ( J:86207 )

• at P1, the cerebral cortex is decreased in size compared to in wild-type mice

• at P1, the cerebral cortex lacks pial vasculature and exhibits cortical degeneration unlike in wild-type mice

• mice exhibit altered cortical neuronal organization compared with wild-type mice

neuron degeneration ( J:86207 )

• at E13.5, mice exhibit neuron degeneration in the forebrain unlike wild-type mice

• mice exhibit neuron degeneration mainly in the subventricular zone unlike wild-type mice

• at E15.5, mice exhibit overt and anterior specific cortical neuronal degeneration unlike wild-type mice

abnormal neuron physiology ( J:86207 )

• by E15.5, mice exhibit an increase in neuron apoptosis in the cortex compared with wild-type mice

abnormal neuron proliferation ( J:86207 )

• mice exhibit a 25% reduction in proliferating neurons compared with wild-type mice

• at E13.5, mice exhibit a 60% reduction in the number of periventricular neurons in the forebrain compared with wild-type mice

cardiovascular system

abnormal brain vasculature morphology ( J:86207 )

• at P1, the cerebral cortex lacks pial vasculature unlike in wild-type mice

• mice exhibit deficient vascular development in the superficial levels of the cortex near the marginal zone and cortical plate, and in the deep ventricular zone compared with wild-type mice

• mice exhibit defects in blood vessel density compared with wild-type mice

• at P1, mice exhibit a decrease in the number of branch points of blood vessels in the cortex and forebrain while the distance between branch points is increased compared with wild-type mice

abnormal retina vasculature morphology ( J:86207 )

• at P1, sprouting angiogenesis into the inner plexiform layer is absent unlike in wild-type mice

abnormal vascular branching morphogenesis ( J:86207 )

• at P1, mice exhibit a decrease in the number of branch points of blood vessels in the cortex and forebrain while the distance between branch points is increased compared with wild-type mice

decreased angiogenesis ( J:86207 )

• at E15.5, decreased vessel density and lack of sprouting is pronounced compared to in wild-type mice

behavior/neurological

absent gastric milk in neonates ( J:86207 )

abnormal motor capabilities/coordination/movement ( J:86207 )

• neonates exhibit spastic uncontrolled movements unlike wild-type mice

• neonates fail to remain upright when placed in a prone position unlike wild-type mice

homeostasis/metabolism

dehydration ( J:86207 )

• mice die of dehydration within 24 hours of birth

hypoxia ( J:86207 )

• between E11.5 and E13.5 in the forebrain and throughout the CNS by E15.5

craniofacial

abnormal craniofacial morphology ( J:86207 )

• as early as E17.5, mice exhibit abnormal cranial morphology compared with wild-type mice

• neonates exhibit altered cranial morphology compared to in wild-type mice

vision/eye

abnormal retina vasculature morphology ( J:86207 )

• at P1, sprouting angiogenesis into the inner plexiform layer is absent unlike in wild-type mice

cellular

abnormal neuron proliferation ( J:86207 )

• mice exhibit a 25% reduction in proliferating neurons compared with wild-type mice

• at E13.5, mice exhibit a 60% reduction in the number of periventricular neurons in the forebrain compared with wild-type mice

Genotype
MGI:4422199

cn10

• Allelic Composition: Vegfa^tm2Gne/Vegfa⁺; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL

vision/eye

abnormal retina morphology ( J:86207 )

• retinas that lack a proper outer vascular plexus are also thin compared to in wild-type mice

abnormal retina vasculature morphology ( J:86207 )

• at P21, retinas lack a proper outer vascular plexus unlike in wild-type mice

abnormal retina outer nuclear layer morphology ( J:86207 )

• between P5 and 3 weeks of age, mice lack clear development of the outer retinal layer compared to in wild-type mice

abnormal retina outer plexiform layer morphology ( J:86207 )

• at P21, mice lack clear development of the outer plexiform layer unlike in wild-type mice

retina degeneration ( J:86207 )

retina gliosis ( J:86207 )

• at P7, some retinas exhibit an increase in microglia/macrophage numbers near the developing veins compared to in wild-type mice

nervous system

abnormal brain vasculature morphology ( J:86207 )

• vascular density and sprouting angiogenesis in the cerebellum, brain stem, and spinal cord are decreased compared to in wild-type mice

• at P1, mice exhibit a decrease in the number of branch points of blood vessels in the forebrain and cortex while the distance between branch points is increased compared with wild-type mice

decreased brain size ( J:86207 )

• cortical brain size is reduced to in wild-type mice

decreased neuron number ( J:86207 )

• neuronal cellularity in the more superficial cortical layers I-III is decreased compared to in wild-type mice

cardiovascular system

abnormal brain vasculature morphology ( J:86207 )

• vascular density and sprouting angiogenesis in the cerebellum, brain stem, and spinal cord are decreased compared to in wild-type mice

• at P1, mice exhibit a decrease in the number of branch points of blood vessels in the forebrain and cortex while the distance between branch points is increased compared with wild-type mice

abnormal retina vasculature morphology ( J:86207 )

• at P21, retinas lack a proper outer vascular plexus unlike in wild-type mice

abnormal vascular branching morphogenesis ( J:86207 )

• at P1, mice exhibit a decrease in the number of branch points of blood vessels in the forebrain and cortex while the distance between branch points is increased compared with wild-type mice

decreased angiogenesis ( J:86207 )

• in the cerebellum, brain stem, and spinal cord

Genotype
MGI:4418463

cn11

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd

immune system

decreased inflammatory response ( J:107682 )

• TPA-treated ears exhibit reduced inflammatory infiltration and edema compared with similarly treated wild-type cells

Genotype
MGI:4418501

cn12

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6

mortality/aging

mortality/aging ( J:148597 )

N • mice exhibit normal LPS-induced mortality

immune system

immune system phenotype ( J:148597 )

N • mice exhibit normal LPS-induced mortality

Genotype
MGI:5444293

cn13

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * FVB/N

homeostasis/metabolism

abnormal wound healing ( J:189044 )

• during the early phase of skin wound healing, mice exhibit reduced amount, cellularity and vascularization of granulation tissue compared with control mice

• during the early to middle stage of wound healing, vascularization is increased compared to in control mice

Genotype
MGI:7343722

cn14

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129/Sv * C3H * C57BL/6

craniofacial

abnormal mandible morphology ( J:309228 )

• at E14.5, E16.5, and E18.5, intramembranous ossification is reduced in the anterior, middle and posterior mandible

• however, no micrognathia is observed

abnormal maxilla morphology ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior maxilla

abnormal palatal mesenchymal cell proliferation ( J:309228 )

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

abnormal secondary palate development ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

• vascularization of the palatal shelves is impaired, with reduced vessel formation at E13.5, less vascular channels and decreased vascular branching at E14.5, and markedly reduced PECAM localization within both anterior and posterior palatal shelves at E15.5

• vascular smooth muscle investment of the palatine artery is absent at E14.5 and appears reduced and only seen 50% of the time at E15.5

• apoptosis remains normal during palatogenesis from E12.5 to E15.5

abnormal palatal shelf bone ossification ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior palatal shelves

abnormal palatal shelf elevation ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation and elevation above the tongue whereas control shelves have elevated and apposed

• at E15.5, palatal shelves are inconsistently elevated whereas control shelves are undergoing fusion as indicated by dissolution of the medial edge epithelium (MEE)

palatal shelves fail to meet at midline ( J:309228 )

decreased palatal shelf size ( J:309228 )

• at E12.5 and 13.5, palatal shelf width, defined as the length from the hinge of the palatal shelf to the tip of the medial edge epithelium (MEE), is significantly reduced both anteriorly and posteriorly

palatal shelf hypoplasia ( J:309228 )

• at E15.5, palatal shelves are hypoplastic

cardiovascular system

abnormal vascular development ( J:309228 )

• at E13.5, E14.5 and E15.5, PECAM immunohistochemistry showed reduced vessel development and branching in both the anterior and posterior palatal shelves

poor arterial differentiation ( J:309228 )

• vascular smooth muscle investment of the palatine artery is absent at E14.5 and appears reduced and only seen 50% of the time at E15.5

skeleton

abnormal mandible morphology ( J:309228 )

• at E14.5, E16.5, and E18.5, intramembranous ossification is reduced in the anterior, middle and posterior mandible

• however, no micrognathia is observed

abnormal maxilla morphology ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior maxilla

abnormal intramembranous bone ossification ( J:309228 )

• at E14.5, mesenchymal condensations within the maxilla ossification centers are reduced in size

• at E16.5, maxillary and palatine bones exhibit less ossification and poor bony ingrowth

• at E18.5, ossification of the maxillary bone is insufficient

• at E14.5, E16.5, and E18.5, ossification is reduced in the anterior, middle and posterior mandible

abnormal palatal shelf bone ossification ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior palatal shelves

digestive/alimentary system

abnormal palatal mesenchymal cell proliferation ( J:309228 )

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

abnormal secondary palate development ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

• vascularization of the palatal shelves is impaired, with reduced vessel formation at E13.5, less vascular channels and decreased vascular branching at E14.5, and markedly reduced PECAM localization within both anterior and posterior palatal shelves at E15.5

• vascular smooth muscle investment of the palatine artery is absent at E14.5 and appears reduced and only seen 50% of the time at E15.5

• apoptosis remains normal during palatogenesis from E12.5 to E15.5

abnormal palatal shelf bone ossification ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior palatal shelves

abnormal palatal shelf elevation ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation and elevation above the tongue whereas control shelves have elevated and apposed

• at E15.5, palatal shelves are inconsistently elevated whereas control shelves are undergoing fusion as indicated by dissolution of the medial edge epithelium (MEE)

palatal shelves fail to meet at midline ( J:309228 )

decreased palatal shelf size ( J:309228 )

• at E12.5 and 13.5, palatal shelf width, defined as the length from the hinge of the palatal shelf to the tip of the medial edge epithelium (MEE), is significantly reduced both anteriorly and posteriorly

palatal shelf hypoplasia ( J:309228 )

• at E15.5, palatal shelves are hypoplastic

growth/size/body

abnormal palatal mesenchymal cell proliferation ( J:309228 )

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

abnormal secondary palate development ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

• vascularization of the palatal shelves is impaired, with reduced vessel formation at E13.5, less vascular channels and decreased vascular branching at E14.5, and markedly reduced PECAM localization within both anterior and posterior palatal shelves at E15.5

• vascular smooth muscle investment of the palatine artery is absent at E14.5 and appears reduced and only seen 50% of the time at E15.5

• apoptosis remains normal during palatogenesis from E12.5 to E15.5

abnormal palatal shelf bone ossification ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior palatal shelves

abnormal palatal shelf elevation ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation and elevation above the tongue whereas control shelves have elevated and apposed

• at E15.5, palatal shelves are inconsistently elevated whereas control shelves are undergoing fusion as indicated by dissolution of the medial edge epithelium (MEE)

palatal shelves fail to meet at midline ( J:309228 )

decreased palatal shelf size ( J:309228 )

• at E12.5 and 13.5, palatal shelf width, defined as the length from the hinge of the palatal shelf to the tip of the medial edge epithelium (MEE), is significantly reduced both anteriorly and posteriorly

palatal shelf hypoplasia ( J:309228 )

• at E15.5, palatal shelves are hypoplastic

Genotype
MGI:2183820

cn15

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

mortality/aging

postnatal lethality, incomplete penetrance ( J:52793 )

• 38% mortality at day 7 after birth when cre expression is induced with IFN-alpha at days 3, 5, and 7 postnatally

growth/size/body

decreased body size ( J:52793 )

• seen when Cre expression is induced by IFN-alpha at birth

postnatal growth retardation ( J:52793 )

• 52% of mice that survive past P7 when Cre expression is induced with IFN-alpha at days 3,5, and 7 postnatally are growth retarded

• however, when IFN-alpha is administered to 6 and 10 week old mice (to induce Cre expression), there are no significant changes in body mass

liver/biliary system

abnormal liver development ( J:52793 )

• seen when Cre expression is induced with IFN-alpha at birth; hepatocytes of 14 day old mutants are small and rounded and the hepatic sinusoidal architecture remains immature, with persistence of twin cell hepatic plates

• many sinusoids contain prominent eosinophilic histiocytes

hematopoietic system

extramedullary hematopoiesis ( J:52793 )

• 14 day old mutants treated with IFN-alpha to induce Cre expression exhibit increased extramedullary hematopoiesis

Genotype
MGI:5471120

cn16

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Tg(Tnnt2-cre)5Blh/0
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:193198 )

• complete lethality is observed after E15.5

growth/size/body

decreased body size ( J:193198 )

• at E15.5, mutants are runted

cardiovascular system

cardiovascular system phenotype ( J:193198 )

N

abnormal angiogenesis ( J:193198 )

• at E12.5, the peritruncal area and ventricular septum lack angiogenic sprouts or coronary plexuses that are observed in controls

myocardium necrosis ( J:193198 )

abnormal coronary vessel morphology ( J:193198 )

abnormal coronary artery morphology ( J:193198 )

• by E14.5, mutants have only a few immature myocardial coronary arteries

abnormal coronary vein morphology ( J:193198 )

• dilated subepicardial veins at E14.5

abnormal heart septum morphology ( J:193198 )

• at E15.5, mutants have necrotic or ruptured septa

thin ventricular wall ( J:193198 )

heart hemorrhage ( J:193198 )

• at E15.5, mutants display cardiac hemorrhages

muscle

myocardium necrosis ( J:193198 )

Genotype
MGI:3840960

cn17

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129/Sv * C57BL/6J * SJL/J

cardiovascular system

abnormal vascular branching morphogenesis ( J:147285 )

• while the capillary network and axial artery are formed in the limb, capillary branching is reduced resulting in formation of a sparse network

Genotype
MGI:4440740

cn18

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; Tg(SFTPC-cre)#Mliu/0
• Genetic Background: involves: 129/Sv * ICR

mortality/aging

abnormal induced morbidity/mortality ( J:158566 )

• after intestinal ischemia/reperfusion (IIR) injury in 7- to 10-week old animals, mortality at 24 hours is 15% compared to 25% in wild-type controls

respiratory system

respiratory system phenotype ( J:158566 )

N • 7-10 week-old mutants show normal lung morphology; blood gas analyses and bronchoalveolar lavage for total and differential cell counts are not different from controls

abnormal lung morphology ( J:158566 )

• acute lung injury (ALI) is ameliorated in 7- to 10-week-old mutants after IIR

• fibrin deposition is rare along alveolar septa and absent within alveolar spaces after IIR in contrast to wild-type at 7 to 10 weeks where dense deposits of fibrin are detected in small vessels and along alveolar septa

pulmonary edema ( J:158566 )

• interstitial edema is lower in mutants after IIR compared to controls at 7 to 10 weeks

abnormal respiratory system physiology ( J:158566 )

• during acute lung injury effected by IIR in 7- to 10-week old animals, epithelial cell death via caspase-dependent mechanisms is significantly higher in mutants than in wild-type controls

abnormal pulmonary circulation ( J:158566 )

• pulmonary vascular permeability is significantly lower than in wild-type controls at 7 to 10 weeks of age

lung inflammation ( J:158566 )

• following IIR in 7- to 10-week old animals, inflammatory mononuclear cell infiltration is significantly reduced compare to wild-type controls

emphysema ( J:158566 )

• emphysema is detected in animals at 28- to 32-weeks of age; significant airspace enlargement is seen histologically and increased lung volume is observed in some cases compared to wild-type mice

abnormal lung compliance ( J:158566 )

homeostasis/metabolism

pulmonary edema ( J:158566 )

• interstitial edema is lower in mutants after IIR compared to controls at 7 to 10 weeks

cardiovascular system

abnormal pulmonary circulation ( J:158566 )

• pulmonary vascular permeability is significantly lower than in wild-type controls at 7 to 10 weeks of age

immune system

lung inflammation ( J:158566 )

• following IIR in 7- to 10-week old animals, inflammatory mononuclear cell infiltration is significantly reduced compare to wild-type controls