Strain Name:

B6;129-Vegfatm1Pec/Mmjax

Availability:

Cryopreserved - Ready for recovery     Available at the JAX MMRRC

Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for information about B6;129-Vegfatm1Pec/Mmjax MMRRC Stock Number 034407.
These VEGF120 mice express a VEGF isoform that lacks exons 6 and 7 (including the extracellular matrix binding structures) resulting in a protein that is highly soluble. Most homozygotes die shortly after birth and exhibit severe retinal vascular defects, delayed periendothelial cell recruitment and reduced numbers of pericytes. This mutant mouse strain may be useful in studies of retinal vascular outgrowth and patterning.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6;129-Vegfatm1Pec/Mmnc    (Changed: 01-AUG-11 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
Generation+pN1
Generation Definitions
 
Donating Investigator Patricia D'Amore,   Schepens Eye Research Institute

Description

Heterozygote: Heterozygous mice are viable, fertile and normal in size .

Homozygote: These VEGF120 mice express a VEGF isoform that lacks exons 6 and 7 (including the extracellular matrix binding structures) resulting in a protein that is highly soluble. The majority of homozygous pups die shortly after birth due to cardiorespiratory distress; survivors do not live beyond two weeks of age due to impaired angiogenesis resulting in cardiac failure. Homozygotes exhibit severe retinal vascular defects including a primitive vascular labyrinth at post natal day 5 (P5), delayed periendothelial cell recruitment and reduced numbers of pericytes. In mice that survive to P9, the capillary bed covers two thirds of the retina. Arteriole and venule development is reduced and capillary number is increased. Capillaries are dilated and fragile resulting in hemorrhages. Hyaloid arteries appear dilated and tortuous with no connections to the retinal vasculature. Hyaloid regression is not observed by P9. Numbers of renal and cornary arteries are reduced. This mutant mouse strain may be useful in studies of retinal vascular outgrowth and patterning.

The Donating Investigator reports that very few mice survive beyond post natal day 1.

Development
A targeting vector containing a loxP-flanked neomycin cassette was used to replace exons 6 and 7. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1 derived R1 embryonic stem (ES) cells. Transient Cre expression in targeted cells excised the neo cassette. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred to C57BL/6 and then maintained by sibling mating. The VEGF 120 isoform lacks exons 6 and 7, which includes the extracellular matrix binding structures and is highly soluble. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Information

  Control
   Wild-type from the colony (approximate)
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Vegfa
016971   B6.Cg-Vegfatm3.1Pec/Mmjax
016972   B6;129-Vegfatm4Pec/Mmjax
005705   FVB-Tg(KRT14-Vegfa)3Dtm/J
View Strains carrying other alleles of Vegfa     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
DiGeorge Syndrome; DGS
Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.
Respiratory Distress Syndrome in Premature Infants
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Microvascular Complications of Diabetes, Susceptibility to, 1; MVCD1   (VEGFA)
Vascular Endothelial Growth Factor A; VEGFA   (VEGFA)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Vegfatm1Pec/Vegfatm1Pec

        involves: 129S1/Sv * 129X1/SvJ
  • mortality/aging
  • complete postnatal lethality
    • those surviving the neonatal period die before P14 (exhibit 51% survival at P1, 27% at P4-P6, 6% at P9 and 0.5% at P12)   (MGI Ref ID J:56003)
  • partial neonatal lethality
    • about half die within a few hours of birth because of bleeding in several organs   (MGI Ref ID J:56003)
    • neonates die shortly after birth because of cardio-respiratory distress   (MGI Ref ID J:75507)
  • growth/size/body phenotype
  • decreased body weight
    • neonates surviving the perinatal period have normal body weights at birth but fail to gain weight   (MGI Ref ID J:56003)
  • cardiovascular system phenotype
  • abnormal blood vessel morphology   (MGI Ref ID J:56003)
    • about 50% of neonates exhibit severe DiGeorge syndrome-like vessel malformations   (MGI Ref ID J:81698)
    • vascular densities in the interventricular septum are lower in neonates that die in the perinatal period and the vessels are grossly abnormal and dilated   (MGI Ref ID J:81698)
    • abnormal artery morphology   (MGI Ref ID J:81698)
      • fewer renal arteries   (MGI Ref ID J:75507)
      • abnormal arteriole morphology
        • fewer and smaller arterioles in the retina   (MGI Ref ID J:75507)
        • less than half of the number of arterioles grow out over only 35% of the retina and 53% of the vascular bed   (MGI Ref ID J:75507)
      • abnormal branchial arch artery morphology
        • E14.5 embryos and neonates have remodeling defects of the 4th, 6th and, less frequently, 3rd pharyngeal arch arteries   (MGI Ref ID J:81698)
        • while the 3rd, 4th and 6th pharyngeal arch arteries are present by E10-10.5, subsequent malformations include hypoplasia, an irregular lumen size, and signs of regression in vessels that should normally persist   (MGI Ref ID J:81698)
        • abnormal fourth branchial arch artery morphology
          • malformations of the 4th arch artery include a persistence of the carotid duct segment between the left carotid and subclavian artery and a descending aorta   (MGI Ref ID J:81698)
        • abnormal sixth branchial arch artery morphology
          • abnormal development of the 6th arch artery; hypoplasia of the pulmonary trunk or malformations of the ductus arteriosus leading to an absent or right-sided ductus   (MGI Ref ID J:81698)
        • abnormal third branchial arch artery morphology   (MGI Ref ID J:81698)
      • abnormal carotid artery morphology
        • malformations of the 3rd arch artery result in a double left or right carotid artery   (MGI Ref ID J:81698)
      • abnormal coronary artery morphology
        • hearts contain fewer coronary vessels, which show less smooth muscle alpha-actin staining   (MGI Ref ID J:56003)
        • fewer coronary arteries   (MGI Ref ID J:75507)
      • abnormal kidney arterial blood vessel morphology
        • fewer SMA-stained kidney arteries are detected at all postnatal ages relative to wild-type controls   (MGI Ref ID J:111504)
        • although lobar arteries develop normally, further branching into arcuate, interlobular, and afferent/efferent arterioles progressively   (MGI Ref ID J:111504)
        • at P0.5 and P3, the number of renin-expressing branch points per kidney section is reduced relative to that in wild-type kidneys   (MGI Ref ID J:111504)
        • abnormal kidney afferent arteriole morphology
          • by P6, the number of afferent arterioles is reduced to ~50% of that in wild-type kidneys   (MGI Ref ID J:111504)
        • abnormal kidney efferent arteriole morphology
          • by P6, the number of efferent arterioles is reduced to ~50% of that in wild-type kidneys   (MGI Ref ID J:111504)
        • abnormal kidney interlobular artery morphology
          • by P6, the number of interlobular arteries is reduced to one-third of that in wild-type kidneys   (MGI Ref ID J:111504)
      • aorta pulmonary collateral arteries
        • observe aortico-pulmonary collateral arteries   (MGI Ref ID J:81698)
      • cervical aortic arch
        • the type-B interruption is associated with persistence of the ductus caroticus, resulting in a cervical aortic arch   (MGI Ref ID J:81698)
      • double aortic arch
        • malformations of the 4th arch artery include a double aortic arch   (MGI Ref ID J:81698)
      • interrupted aortic arch
        • malformations of the 4th arch artery include type-B left 4th aortic arch interruption   (MGI Ref ID J:81698)
      • persistent ductus caroticus
        • persistence of the cartoid duct segment between the left carotid and subclavian artery   (MGI Ref ID J:81698)
        • the type-B interruption is associated with persistence of the ductus caroticus, resulting in a cervical aortic arch   (MGI Ref ID J:81698)
      • persistent right dorsal aorta
        • about 10% of embryos exhibit a dominant right dorsal aorta   (MGI Ref ID J:81698)
      • pulmonary trunk hypoplasia
        • hypoplasia of the pulmonary trunk in E13.5-14.5 embryos   (MGI Ref ID J:81698)
      • retroesophageal right subclavian artery
        • malformations of the 4th arch artery include a right 4th arch interruption together with an aberrant subclavian artery, resulting in a retroesophageal right subclavian artery   (MGI Ref ID J:81698)
      • right aortic arch
        • malformations of the 4th arch artery include a right-sided aortic arch   (MGI Ref ID J:81698)
    • abnormal capillary morphology
      • do not observe a change in capillary density from birth to P12 as in wild-type, indicating a 400% reduction in density   (MGI Ref ID J:56003)
      • defective capillary vessel formation results in larger inter-capillary distances in hearts and an increase in myocyte-to-capillary ratios at P12   (MGI Ref ID J:56003)
      • capillaries in hearts are irregular, tortuous and slightly dilated, indicative of incomplete vessel remodeling   (MGI Ref ID J:56003)
      • capillary densities in skeletal muscles are also decreased   (MGI Ref ID J:56003)
      • capillary density and size in the septum are less affected in those mice that die 2 weeks after birth (rather than perinatally)   (MGI Ref ID J:81698)
      • exhibit more numerous, dilated and fragile capillaries in the central retina   (MGI Ref ID J:75507)
      • abnormal glomerular capillary morphology
        • at P0.5, mutant glomeruli exhibit fewer and disordered capillary loops, unlike wild-type glomeruli   (MGI Ref ID J:111504)
        • abnormal glomerular capillary endothelium morphology
          • at E15.5 to P6, fewer glomeruli are vascularized, as revealed by CD34-staining   (MGI Ref ID J:111504)
          • by P6, ~40% fewer glomeruli contain CD34-positive endothelial cells; however, endothelial fenestration occurs as in wild-type controls   (MGI Ref ID J:111504)
          • endothelial cells appear to detach from their underlying basement membrane and show signs of cellular degeneration and death (blebbing, vacuolization, nuclear disintegration)   (MGI Ref ID J:111504)
        • decreased glomerular capillary number
          • at E15.5 to P6, the number of laminin-positive capillary loops per glomerulus is reduced relative to that in wild-type controls   (MGI Ref ID J:111504)
          • when capillary loops form, they fail to expand into a complex tuft and eventually disintegrate   (MGI Ref ID J:111504)
      • abnormal peritubular capillary morphology
        • by P6, peritubular capillaries remain dilated, appear tortuous and irregular, and lack symmetric patterning   (MGI Ref ID J:111504)
        • endothelial cells in peritubular capillaries contain luminal cytoplasmic protrusions and blebs or appear thin and elongated, unlike wild-type peritubular capillaries which contain intact, regular, and tightly interacting endothelial cells   (MGI Ref ID J:111504)
        • at P6, the distance between neighboring peritubular capillaries is enlarged, suggesting kidney ischemia   (MGI Ref ID J:111504)
    • abnormal kidney blood vessel morphology
      • capillary growth in renal glomeruli is retarded   (MGI Ref ID J:56003)
      • fewer renal arteries   (MGI Ref ID J:75507)
      • abnormal glomerular capillary morphology
        • at P0.5, mutant glomeruli exhibit fewer and disordered capillary loops, unlike wild-type glomeruli   (MGI Ref ID J:111504)
        • abnormal glomerular capillary endothelium morphology
          • at E15.5 to P6, fewer glomeruli are vascularized, as revealed by CD34-staining   (MGI Ref ID J:111504)
          • by P6, ~40% fewer glomeruli contain CD34-positive endothelial cells; however, endothelial fenestration occurs as in wild-type controls   (MGI Ref ID J:111504)
          • endothelial cells appear to detach from their underlying basement membrane and show signs of cellular degeneration and death (blebbing, vacuolization, nuclear disintegration)   (MGI Ref ID J:111504)
        • decreased glomerular capillary number
          • at E15.5 to P6, the number of laminin-positive capillary loops per glomerulus is reduced relative to that in wild-type controls   (MGI Ref ID J:111504)
          • when capillary loops form, they fail to expand into a complex tuft and eventually disintegrate   (MGI Ref ID J:111504)
      • abnormal kidney arterial blood vessel morphology
        • fewer SMA-stained kidney arteries are detected at all postnatal ages relative to wild-type controls   (MGI Ref ID J:111504)
        • although lobar arteries develop normally, further branching into arcuate, interlobular, and afferent/efferent arterioles progressively   (MGI Ref ID J:111504)
        • at P0.5 and P3, the number of renin-expressing branch points per kidney section is reduced relative to that in wild-type kidneys   (MGI Ref ID J:111504)
        • abnormal kidney afferent arteriole morphology
          • by P6, the number of afferent arterioles is reduced to ~50% of that in wild-type kidneys   (MGI Ref ID J:111504)
        • abnormal kidney efferent arteriole morphology
          • by P6, the number of efferent arterioles is reduced to ~50% of that in wild-type kidneys   (MGI Ref ID J:111504)
        • abnormal kidney interlobular artery morphology
          • by P6, the number of interlobular arteries is reduced to one-third of that in wild-type kidneys   (MGI Ref ID J:111504)
      • abnormal peritubular capillary morphology
        • by P6, peritubular capillaries remain dilated, appear tortuous and irregular, and lack symmetric patterning   (MGI Ref ID J:111504)
        • endothelial cells in peritubular capillaries contain luminal cytoplasmic protrusions and blebs or appear thin and elongated, unlike wild-type peritubular capillaries which contain intact, regular, and tightly interacting endothelial cells   (MGI Ref ID J:111504)
        • at P6, the distance between neighboring peritubular capillaries is enlarged, suggesting kidney ischemia   (MGI Ref ID J:111504)
    • abnormal pericyte morphology
      • fewer pericytes are detected around peritubular capillaries relative to wild-type kidneys   (MGI Ref ID J:111504)
    • abnormal retinal vasculature morphology
      • outgrowth of capillaries and pericyte coverage is impaired in the retinal vasculature, which remains more immaturely remodeled   (MGI Ref ID J:56003)
      • only a primitive vascular labyrinth of capillary-like vessels with uniform size develop by P5   (MGI Ref ID J:75507)
      • periendothelial cell (PEC) recruitment is delayed, with only scattered PECs detected in and around the optic disc   (MGI Ref ID J:75507)
      • the capillary bed covers the retina only over 2/3 in the small fraction of mice that survive to P9   (MGI Ref ID J:75507)
      • exhibit more numerous and dilated capillaries in the central retina   (MGI Ref ID J:75507)
      • fewer periendothelial cells surround the arterioles, venules, and capillaries   (MGI Ref ID J:75507)
    • abnormal vascular regression
      • exhibit signs of regression in vessels of the pharyngeal arch that should normally persist   (MGI Ref ID J:81698)
    • abnormal venule morphology
      • fewer and smaller venules in the retina   (MGI Ref ID J:75507)
      • only half of the number of venules are seen in the retina at P9, but have a normal lumen size, and they grow out over only 52% of the retinal radius, but over 80% of the vascular bed   (MGI Ref ID J:75507)
    • decreased angiogenesis
      • defects most profound in the subendomyocardium   (MGI Ref ID J:56003)
      • capillary and coronary angiogenesis is impaired in the right ventricle and in the atria   (MGI Ref ID J:56003)
  • abnormal cardiovascular system physiology   (MGI Ref ID J:56003)
    • abnormal cardiac muscle relaxation
      • depressed left ventricular relaxation   (MGI Ref ID J:56003)
    • abnormal impulse conducting system conduction
      • electrical pulse shows signs of dispersion and heterogeneity   (MGI Ref ID J:56003)
      • abnormal ST segment
        • exhibit ST-segment depressions in mice at rest   (MGI Ref ID J:56003)
        • rapidly develop considerable ST-segment elevations when ventilation is stopped   (MGI Ref ID J:56003)
      • abnormal T wave
        • exhibit T-wave inversions in mice at rest   (MGI Ref ID J:56003)
      • prolonged QRS complex duration
        • prolonged QRS interval at P6   (MGI Ref ID J:56003)
      • prolonged QT interval   (MGI Ref ID J:56003)
    • cardiac ischemia
      • myocardial ischemia; regional blood flow through the myocardium at P6 is 0.7 ml/min per g compared to 2.9 in wild-type   (MGI Ref ID J:56003)
    • decreased cardiac muscle contractility
      • exhibit dysmorphic, weak heart contractions   (MGI Ref ID J:56003)
      • depressed left ventricular contractility; enlarged systolic left ventricular and diastolic left ventricular diameters, impaired fractional shortening, and reduced aortic outflow velocity   (MGI Ref ID J:56003)
      • suffer severe left ventricular pump failure and show signs of right ventricular failure, including accumulation of ascitic fluid and increased liver-to-body weight   (MGI Ref ID J:56003)
    • decreased heart rate
      • slower heart rates in conscious P6 mice   (MGI Ref ID J:56003)
    • decreased left ventricle systolic pressure
      • left ventricular pressure is further reduced during periods of spontaneous arrhythmia   (MGI Ref ID J:56003)
    • hemorrhage
      • about half die within a few hours of birth because of bleeding in several organs   (MGI Ref ID J:56003)
      • retinal hemorrhage
        • fragile capillaries in the retina cause hemorrhages   (MGI Ref ID J:75507)
    • irregular heartbeat   (MGI Ref ID J:56003)
  • abnormal heart morphology   (MGI Ref ID J:56003)
    • mutants that die in the perinatal period exhibit a wide spectrum of cardiac defects, including Tetralogy of Fallot, however do not observe cardiac defects in those that survive postnatally   (MGI Ref ID J:81698)
    • abnormal coronary vessel morphology
      • vascular densities in the interventricular septum are lower in neonates that die in the perinatal period and the vessels are grossly abnormal and dilated   (MGI Ref ID J:81698)
      • abnormal coronary artery morphology
        • hearts contain fewer coronary vessels, which show less smooth muscle alpha-actin staining   (MGI Ref ID J:56003)
        • fewer coronary arteries   (MGI Ref ID J:75507)
    • abnormal myocardial fiber morphology
      • at P6, cardiomyocytes progressively lose perinuclear myofibrils, exhibit a reduction in the number of gap junctions between cardiomyocytes, either reduced or disorganized desmin, distorted nuclei with increased amounts of glycogen, irregular mini-mitochondria, and increased levels of fetal genes that are re-introduced during the course of ischemic heart disease   (MGI Ref ID J:56003)
      • enlarged myocardial fiber
        • cardiomyoctes are slightly larger at P12   (MGI Ref ID J:56003)
      • myocardial fiber degeneration
        • detect atrophy and degeneration of cardiomyocytes beyond P6; cardiomyocytes show loss of myofibrils, costamere disruption, lipid-like inclusions, irregular nuclear shape, and a nonspecified cytoplasm filled with necrotic remnants and cellular debris   (MGI Ref ID J:56003)
    • enlarged heart   (MGI Ref ID J:56003)
    • overriding aortic valve   (MGI Ref ID J:81698)
    • persistent truncus arteriosis   (MGI Ref ID J:81698)
    • ventricular septal defect
      • ventricular septal defect   (MGI Ref ID J:81698)
  • behavior/neurological phenotype
  • lethargy
    • become progressively lethargic   (MGI Ref ID J:56003)
  • muscle phenotype
  • abnormal cardiac muscle relaxation
    • depressed left ventricular relaxation   (MGI Ref ID J:56003)
  • abnormal myocardial fiber morphology
    • at P6, cardiomyocytes progressively lose perinuclear myofibrils, exhibit a reduction in the number of gap junctions between cardiomyocytes, either reduced or disorganized desmin, distorted nuclei with increased amounts of glycogen, irregular mini-mitochondria, and increased levels of fetal genes that are re-introduced during the course of ischemic heart disease   (MGI Ref ID J:56003)
    • enlarged myocardial fiber
      • cardiomyoctes are slightly larger at P12   (MGI Ref ID J:56003)
    • myocardial fiber degeneration
      • detect atrophy and degeneration of cardiomyocytes beyond P6; cardiomyocytes show loss of myofibrils, costamere disruption, lipid-like inclusions, irregular nuclear shape, and a nonspecified cytoplasm filled with necrotic remnants and cellular debris   (MGI Ref ID J:56003)
  • abnormal sarcomere morphology
    • sarcomere rarefication   (MGI Ref ID J:56003)
  • decreased cardiac muscle contractility
    • exhibit dysmorphic, weak heart contractions   (MGI Ref ID J:56003)
    • depressed left ventricular contractility; enlarged systolic left ventricular and diastolic left ventricular diameters, impaired fractional shortening, and reduced aortic outflow velocity   (MGI Ref ID J:56003)
    • suffer severe left ventricular pump failure and show signs of right ventricular failure, including accumulation of ascitic fluid and increased liver-to-body weight   (MGI Ref ID J:56003)
  • renal/urinary system phenotype
  • abnormal kidney blood vessel morphology
    • capillary growth in renal glomeruli is retarded   (MGI Ref ID J:56003)
    • fewer renal arteries   (MGI Ref ID J:75507)
    • abnormal glomerular capillary morphology
      • at P0.5, mutant glomeruli exhibit fewer and disordered capillary loops, unlike wild-type glomeruli   (MGI Ref ID J:111504)
      • abnormal glomerular capillary endothelium morphology
        • at E15.5 to P6, fewer glomeruli are vascularized, as revealed by CD34-staining   (MGI Ref ID J:111504)
        • by P6, ~40% fewer glomeruli contain CD34-positive endothelial cells; however, endothelial fenestration occurs as in wild-type controls   (MGI Ref ID J:111504)
        • endothelial cells appear to detach from their underlying basement membrane and show signs of cellular degeneration and death (blebbing, vacuolization, nuclear disintegration)   (MGI Ref ID J:111504)
      • decreased glomerular capillary number
        • at E15.5 to P6, the number of laminin-positive capillary loops per glomerulus is reduced relative to that in wild-type controls   (MGI Ref ID J:111504)
        • when capillary loops form, they fail to expand into a complex tuft and eventually disintegrate   (MGI Ref ID J:111504)
    • abnormal kidney arterial blood vessel morphology
      • fewer SMA-stained kidney arteries are detected at all postnatal ages relative to wild-type controls   (MGI Ref ID J:111504)
      • although lobar arteries develop normally, further branching into arcuate, interlobular, and afferent/efferent arterioles progressively   (MGI Ref ID J:111504)
      • at P0.5 and P3, the number of renin-expressing branch points per kidney section is reduced relative to that in wild-type kidneys   (MGI Ref ID J:111504)
      • abnormal kidney afferent arteriole morphology
        • by P6, the number of afferent arterioles is reduced to ~50% of that in wild-type kidneys   (MGI Ref ID J:111504)
      • abnormal kidney efferent arteriole morphology
        • by P6, the number of efferent arterioles is reduced to ~50% of that in wild-type kidneys   (MGI Ref ID J:111504)
      • abnormal kidney interlobular artery morphology
        • by P6, the number of interlobular arteries is reduced to one-third of that in wild-type kidneys   (MGI Ref ID J:111504)
    • abnormal peritubular capillary morphology
      • by P6, peritubular capillaries remain dilated, appear tortuous and irregular, and lack symmetric patterning   (MGI Ref ID J:111504)
      • endothelial cells in peritubular capillaries contain luminal cytoplasmic protrusions and blebs or appear thin and elongated, unlike wild-type peritubular capillaries which contain intact, regular, and tightly interacting endothelial cells   (MGI Ref ID J:111504)
      • at P6, the distance between neighboring peritubular capillaries is enlarged, suggesting kidney ischemia   (MGI Ref ID J:111504)
  • abnormal loop of Henle morphology
    • at P6, fewer but often enlarged and tortuous loops of Henle are observed, unlike in wild-type kidneys   (MGI Ref ID J:111504)
    • ultrastructural signs of ischemia are detected in the loops of Henle, unlike in wild-type kidneys   (MGI Ref ID J:111504)
  • abnormal mesangial cell morphology
    • mesangial cells gradually disappear as glomeruli become sclerotic and loose their capillary network   (MGI Ref ID J:111504)
  • abnormal nephrogenic zone morphology
    • at P3, the nephrogenic cortex is reduced by ~25% relative to that in wild-type kidneys   (MGI Ref ID J:111504)
  • abnormal proximal convoluted tubule morphology
    • at P0.5, P3, and P6, fewer proximal convoluted tubules are observed relative to wild-type controls   (MGI Ref ID J:111504)
    • ultrastructural signs of ischemia are detected in the proximal tubules, unlike in wild-type kidneys   (MGI Ref ID J:111504)
    • in contrast, distal convoluted tubules are of normal size, number and morphology   (MGI Ref ID J:111504)
    • dilated proximal convoluted tubules
      • at P3 and P6, proximal convoluted tubules appear enlarged relative to those in wild-type kidneys   (MGI Ref ID J:111504)
  • abnormal renal glomerulus basement membrane morphology
    • at P0.5, the GBM often displays a variable shape and thickness, and appears more irregular and tortuous   (MGI Ref ID J:111504)
    • abnormal renal glomerulus basement membrane thickness
      • the GBM often displays a variable thickness in mature glomeruli after E17.5   (MGI Ref ID J:111504)
  • decreased renal glomerular filtration rate
    • at P6, glomerular filtration is impaired, as shown by elevated levels of plasma creatinine and urea   (MGI Ref ID J:111504)
    • GFR cannot be determined by measuring creatinine clearance, as mutant neonates are fragile   (MGI Ref ID J:111504)
    • after i.v injection of neutral horseradish peroxidase (HRP), abundant HRP leaks through the glomerular filter into the urine and is detected on the brush border, in microvilli, and in intracellular endocytic vesicles in proximal tubules, unlike in wild-type kidneys   (MGI Ref ID J:111504)
  • decreased renal glomerulus number
    • at P0.5, P3, and P6, homozygotes display ~25% fewer glomeruli/kidney section relative to wild-type controls   (MGI Ref ID J:111504)
    • however, glomerular density (i.e., glomeruli per mm2) is not reduced because kidneys are smaller   (MGI Ref ID J:111504)
  • expanded mesangial matrix
    • most sclerotic glomeruli accumulate an unusual amount of collagen type IV, fibrin, fibronectin, and laminin   (MGI Ref ID J:111504)
    • excessive matrix deposition is already detectable in fetal mature glomeruli after E17.5   (MGI Ref ID J:111504)
  • glomerulosclerosis
    • at P0.5, P3 and P6, the number of sclerotic/total glomeruli is 0/52 (0%), 7/107 (6.5%), and 18/104 (17%), respectively, unlike in wild-type kidneys where no sclerotic glomeruli are observed   (MGI Ref ID J:111504)
    • at P6, abnormal accumulation of laminin is noted in mutant sclerotic glomeruli but not in mature wild-type glomeruli   (MGI Ref ID J:111504)
    • in sclerotic glomeruli, the entire capillary bed often disappears and is replaced by amorphous granular necrotic debris   (MGI Ref ID J:111504)
    • however, parietal epithelial cells in the capsule of Bowman and podocytes remain normal in most glomeruli and persist even when glomeruli become sclerotic   (MGI Ref ID J:111504)
  • pale kidney
    • mutant kidneys are generally paler than wild-type   (MGI Ref ID J:111504)
  • renal glomerulus hypertrophy
    • by P6, mutant sclerotic glomeruli are ~3-fold larger than mature wild-type glomeruli   (MGI Ref ID J:111504)
  • renal ischemia
    • ultrastructural signs of ischemia (mitochondrial clarification, disrupted mitochondrial cristae, cytoplasmic vacuolization, intracellular edema, swelling, and plasmalemma blebbing) are detected in the proximal tubules and loops of Henle, unlike in wild-type kidneys   (MGI Ref ID J:111504)
    • at P6, the distance between neighboring peritubular capillaries is enlarged, suggesting kidney ischemia   (MGI Ref ID J:111504)
  • small kidney
    • at P0.5, P3, and P6, mutant kidneys are smaller than wild-type   (MGI Ref ID J:111504)
    • however, kidney growth is proportional to that of total body, with no significant differences in kidney/total body weight ratio at P0.5 and P6   (MGI Ref ID J:111504)
  • vision/eye phenotype
  • abnormal retinal vasculature morphology
    • outgrowth of capillaries and pericyte coverage is impaired in the retinal vasculature, which remains more immaturely remodeled   (MGI Ref ID J:56003)
    • only a primitive vascular labyrinth of capillary-like vessels with uniform size develop by P5   (MGI Ref ID J:75507)
    • periendothelial cell (PEC) recruitment is delayed, with only scattered PECs detected in and around the optic disc   (MGI Ref ID J:75507)
    • the capillary bed covers the retina only over 2/3 in the small fraction of mice that survive to P9   (MGI Ref ID J:75507)
    • exhibit more numerous and dilated capillaries in the central retina   (MGI Ref ID J:75507)
    • fewer periendothelial cells surround the arterioles, venules, and capillaries   (MGI Ref ID J:75507)
  • persistence of hyaloid vascular system
    • no signs of hyaloid regression are seen at P9, and the hyaloid vessels appear dilated and tortuous, however the hyaloid arteries do not penetrate the retina or make connections with the retinal vasculature   (MGI Ref ID J:75507)
  • retinal hemorrhage
    • fragile capillaries in the retina cause hemorrhages   (MGI Ref ID J:75507)
  • nervous system phenotype
  • abnormal facial motor nucleus morphology
    • facial motor nuclei appear elongated or dumbbell-shaped   (MGI Ref ID J:94050)
    • in 7 of 9 mutants, one or both facial motor nuclei are shifted anteriorly, however facial nerve is not defasciculated   (MGI Ref ID J:94050)
  • abnormal neuronal migration
    • caudally migrating somata of facial branchiomotor neurons prematurely turns dorsally and dives through the basal plate in ectopic anterior locations   (MGI Ref ID J:94050)
  • decreased neuron number
    • reduced gonadotropin-releasing hormone neurons at E14.5, E15.5 and E18.5   (MGI Ref ID J:175836)
  • increased neuron apoptosis
    • of gonadotropin-releasing hormone neurons   (MGI Ref ID J:175836)
  • craniofacial phenotype
  • abnormal branchial arch artery morphology
    • E14.5 embryos and neonates have remodeling defects of the 4th, 6th and, less frequently, 3rd pharyngeal arch arteries   (MGI Ref ID J:81698)
    • while the 3rd, 4th and 6th pharyngeal arch arteries are present by E10-10.5, subsequent malformations include hypoplasia, an irregular lumen size, and signs of regression in vessels that should normally persist   (MGI Ref ID J:81698)
    • abnormal fourth branchial arch artery morphology
      • malformations of the 4th arch artery include a persistence of the carotid duct segment between the left carotid and subclavian artery and a descending aorta   (MGI Ref ID J:81698)
    • abnormal sixth branchial arch artery morphology
      • abnormal development of the 6th arch artery; hypoplasia of the pulmonary trunk or malformations of the ductus arteriosus leading to an absent or right-sided ductus   (MGI Ref ID J:81698)
    • abnormal third branchial arch artery morphology   (MGI Ref ID J:81698)
  • abnormal coronal suture morphology
    • cranial sutures between the frontal and parietal bones fail to close properly   (MGI Ref ID J:81698)
  • abnormal mandible morphology
    • vascular density in the mandible is significantly reduced and the vessels are abnormally dilated and tortuous   (MGI Ref ID J:81698)
    • short mandible   (MGI Ref ID J:81698)
  • absent incisors
    • 43% lack incisors   (MGI Ref ID J:81698)
  • cleft palate
    • seen in 74% of mutants   (MGI Ref ID J:81698)
  • embryogenesis phenotype
  • abnormal branchial arch artery morphology
    • E14.5 embryos and neonates have remodeling defects of the 4th, 6th and, less frequently, 3rd pharyngeal arch arteries   (MGI Ref ID J:81698)
    • while the 3rd, 4th and 6th pharyngeal arch arteries are present by E10-10.5, subsequent malformations include hypoplasia, an irregular lumen size, and signs of regression in vessels that should normally persist   (MGI Ref ID J:81698)
    • abnormal fourth branchial arch artery morphology
      • malformations of the 4th arch artery include a persistence of the carotid duct segment between the left carotid and subclavian artery and a descending aorta   (MGI Ref ID J:81698)
    • abnormal sixth branchial arch artery morphology
      • abnormal development of the 6th arch artery; hypoplasia of the pulmonary trunk or malformations of the ductus arteriosus leading to an absent or right-sided ductus   (MGI Ref ID J:81698)
    • abnormal third branchial arch artery morphology   (MGI Ref ID J:81698)
  • endocrine/exocrine gland phenotype
  • absent parathyroid glands
    • absent in 4 of 12 neonates, and when present, they are associated with an ectopic thymic lobe   (MGI Ref ID J:81698)
  • homeostasis/metabolism phenotype
  • cyanosis
    • homozyogotes that die in the perinatal period become cyanotic immediately after birth   (MGI Ref ID J:81698)
  • increased blood urea nitrogen level
    • at P6, plasma urea levels are significantly higher than those in wild-type controls   (MGI Ref ID J:111504)
  • increased circulating creatinine level
    • at P6, plasma creatinine levels are significantly higher than those in wild-type controls   (MGI Ref ID J:111504)
  • immune system phenotype
  • abnormal thymus morphology
    • vessel density and total vascular volume are reduced in the thymus   (MGI Ref ID J:81698)
    • athymia
      • 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus   (MGI Ref ID J:81698)
    • ectopic thymus
      • 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus   (MGI Ref ID J:81698)
    • thymus hypoplasia
      • 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus   (MGI Ref ID J:81698)
  • decreased lymphocyte cell number
    • fraction of circulating lymphocytes is decreased   (MGI Ref ID J:81698)
  • skeleton phenotype
  • abnormal coronal suture morphology
    • cranial sutures between the frontal and parietal bones fail to close properly   (MGI Ref ID J:81698)
  • abnormal mandible morphology
    • vascular density in the mandible is significantly reduced and the vessels are abnormally dilated and tortuous   (MGI Ref ID J:81698)
    • short mandible   (MGI Ref ID J:81698)
  • hematopoietic system phenotype
  • abnormal thymus morphology
    • vessel density and total vascular volume are reduced in the thymus   (MGI Ref ID J:81698)
    • athymia
      • 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus   (MGI Ref ID J:81698)
    • ectopic thymus
      • 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus   (MGI Ref ID J:81698)
    • thymus hypoplasia
      • 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus   (MGI Ref ID J:81698)
  • decreased lymphocyte cell number
    • fraction of circulating lymphocytes is decreased   (MGI Ref ID J:81698)
  • digestive/alimentary phenotype
  • cleft palate
    • seen in 74% of mutants   (MGI Ref ID J:81698)
  • respiratory system phenotype
  • abnormal lung development
    • a fraction of newborn homozygotes that die of respiratory distress syndrome exhibit increased alveolar septal thickness and abundant immature PAS+ (glycogen-rich) pneumocytes, indicating lung prematurity   (MGI Ref ID J:77480)
  • aorta pulmonary collateral arteries
    • observe aortico-pulmonary collateral arteries   (MGI Ref ID J:81698)
  • atelectasis
    • in a fraction of newborn homozygotes, lung aeration (percentage of total surface filled with air) fails to increase after birth   (MGI Ref ID J:77480)
  • respiratory distress
    • a fraction of newborn homozygotes die of respiratory distress syndrome   (MGI Ref ID J:77480)
  • thick pulmonary interalveolar septum
    • a fraction of newborn homozygotes that die of respiratory distress syndrome display a significantly increased alveolar septal thickness at birth   (MGI Ref ID J:77480)
  • cellular phenotype
  • abnormal neuronal migration
    • caudally migrating somata of facial branchiomotor neurons prematurely turns dorsally and dives through the basal plate in ectopic anterior locations   (MGI Ref ID J:94050)
  • increased neuron apoptosis
    • of gonadotropin-releasing hormone neurons   (MGI Ref ID J:175836)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Cardiovascular Research
Vascular Defects

Developmental Biology Research
Eye Defects
Internal/Organ Defects
      vasculature

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Vegfatm1Pec
Allele Name targeted mutation 1, Peter Carmeliet
Allele Type Targeted (knock-out)
Common Name(s) VEGF120;
Mutation Made ByDr. Peter Carmeliet,   University of Leuven
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Vegfa, vascular endothelial growth factor A
Chromosome 17
Gene Common Name(s) MVCD1; VEGF; VEGF-A; VEGF120; VEGF164; VEGF188; VPF; Vegf; vascular endothelial growth factor;
Molecular Note Replacement of exons 6 and 7 with a lox-P flanked neomycin cassette. The neomycin cassette was removed prior to blastocyst injection by Cre-mediated recombination in ES cells, resulting in the final allele. A highly soluble isoform of the encoded protein is expressed from this allele. [MGI Ref ID J:56003]

Genotyping

Genotyping Information

Genotyping Protocols

Vegfatm1Pec, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Carmeliet P; Ng YS; Nuyens D; Theilmeier G; Brusselmans K; Cornelissen I; Ehler E; Kakkar VV; Stalmans I; Mattot V; Perriard JC; Dewerchin M; Flameng W; Nagy A; Lupu F; Moons L; Collen D; D'Amore PA; Shima DT. 1999. Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188 [see comments] Nat Med 5(5):495-502. [PubMed: 10229225]  [MGI Ref ID J:56003]

Additional References

Vegfatm1Pec related

Cariboni A; Davidson K; Dozio E; Memi F; Schwarz Q; Stossi F; Parnavelas JG; Ruhrberg C. 2011. VEGF signalling controls GnRH neuron survival via NRP1 independently of KDR and blood vessels. Development 138(17):3723-33. [PubMed: 21828096]  [MGI Ref ID J:175836]

Compernolle V; Brusselmans K; Acker T; Hoet P; Tjwa M; Beck H; Plaisance S; Dor Y; Keshet E; Lupu F; Nemery B; Dewerchin M; Van Veldhoven P; Plate K; Moons L; Collen D; Carmeliet P. 2002. Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med 8(7):702-10. [PubMed: 12053176]  [MGI Ref ID J:77480]

Delalande JM; Natarajan D; Vernay B; Finlay M; Ruhrberg C; Thapar N; Burns AJ. 2014. Vascularisation is not necessary for gut colonisation by enteric neural crest cells. Dev Biol 385(2):220-9. [PubMed: 24262984]  [MGI Ref ID J:205408]

Erskine L; Reijntjes S; Pratt T; Denti L; Schwarz Q; Vieira JM; Alakakone B; Shewan D; Ruhrberg C. 2011. VEGF signaling through neuropilin 1 guides commissural axon crossing at the optic chiasm. Neuron 70(5):951-65. [PubMed: 21658587]  [MGI Ref ID J:174966]

Fantin A; Vieira JM; Gestri G; Denti L; Schwarz Q; Prykhozhij S; Peri F; Wilson SW; Ruhrberg C. 2010. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood 116(5):829-40. [PubMed: 20404134]  [MGI Ref ID J:163512]

Galambos C; Ng YS; Ali A; Noguchi A; Lovejoy S; D'Amore PA; DeMello DE. 2002. Defective pulmonary development in the absence of heparin-binding vascular endothelial growth factor isoforms. Am J Respir Cell Mol Biol 27(2):194-203. [PubMed: 12151311]  [MGI Ref ID J:111235]

Maes C; Carmeliet P; Moermans K; Stockmans I; Smets N; Collen D; Bouillon R; Carmeliet G. 2002. Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF(164) and VEGF(188). Mech Dev 111(1-2):61-73. [PubMed: 11804779]  [MGI Ref ID J:74493]

Mattot V; Moons L; Lupu F; Chernavvsky D; Gomez RA; Collen D; Carmeliet P. 2002. Loss of the VEGF(164) and VEGF(188) isoforms impairs postnatal glomerular angiogenesis and renal arteriogenesis in mice. J Am Soc Nephrol 13(6):1548-60. [PubMed: 12039984]  [MGI Ref ID J:111504]

Ruhrberg C; Gerhardt H; Golding M; Watson R; Ioannidou S; Fujisawa H; Betsholtz C; Shima DT. 2002. Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes Dev 16(20):2684-98. [PubMed: 12381667]  [MGI Ref ID J:79490]

Ruiz de Almodovar C; Coulon C; Salin PA; Knevels E; Chounlamountri N; Poesen K; Hermans K; Lambrechts D; Van Geyte K; Dhondt J; Dresselaers T; Renaud J; Aragones J; Zacchigna S; Geudens I; Gall D; Stroobants S; Mutin M; Dassonville K; Storkebaum E; Jordan BF; Eriksson U; Moons L; D'Hooge R; Haigh JJ; Belin MF; Schiffmann S; Van Hecke P; Gallez B; Vinckier S; Chedotal A; Honnorat J; Thomasset N; Carmeliet P; Meissirel C. 2010. Matrix-binding vascular endothelial growth factor (VEGF) isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1. J Neurosci 30(45):15052-66. [PubMed: 21068311]  [MGI Ref ID J:166454]

Saint-Geniez M; Kurihara T; D'Amore PA. 2009. Role of cell and matrix-bound VEGF isoforms in lens development. Invest Ophthalmol Vis Sci 50(1):311-21. [PubMed: 18757513]  [MGI Ref ID J:146692]

Scherptong RW; Jongbloed MR; Wisse LJ; Vicente-Steijn R; Bartelings MM; Poelmann RE; Schalij MJ; Gittenberger-De Groot AC. 2012. Morphogenesis of outflow tract rotation during cardiac development: The pulmonary push concept. Dev Dyn 241(9):1413-22. [PubMed: 22826212]  [MGI Ref ID J:186546]

Schwarz Q; Gu C; Fujisawa H; Sabelko K; Gertsenstein M; Nagy A; Taniguchi M; Kolodkin AL; Ginty DD; Shima DT; Ruhrberg C. 2004. Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve. Genes Dev 18(22):2822-34. [PubMed: 15545635]  [MGI Ref ID J:94050]

Stalmans I; Lambrechts D; De Smet F; Jansen S; Wang J; Maity S; Kneer P; Von Der Ohe M; Swillen A; Maes C; Gewillig M; Molin DG; Hellings P; Boetel T; Haardt M; Compernolle V; Dewerchin M; Plaisance S; Vlietinck R; Emanuel B; Gittenberger-De Groot AC; Scambler P; Morrow B; Driscol DA; Moons L; Esguerra CV; Carmeliet G; Behn-Krappa A; Devriendt K; Collen D; Conway SJ; Carmeliet P. 2003. VEGF: A modifier of the del22q11 (DiGeorge) syndrome? Nat Med 9(2):173-82. [PubMed: 12539040]  [MGI Ref ID J:81698]

Stalmans I; Ng YS; Rohan R; Fruttiger M; Bouche A; Yuce A; Fujisawa H; Hermans B; Shani M; Jansen S; Hicklin D; Anderson DJ; Gardiner T; Hammes HP; Moons L; Dewerchin M; Collen D; Carmeliet P; D'Amore PA. 2002. Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. J Clin Invest 109(3):327-36. [PubMed: 11827992]  [MGI Ref ID J:75507]

Vieira JM; Schwarz Q; Ruhrberg C. 2007. Selective requirements for NRP1 ligands during neurovascular patterning. Development 134(10):1833-43. [PubMed: 17428830]  [MGI Ref ID J:121420]

Wang H; Geisen P; Wittchen ES; King B; Burridge K; D'Amore PA; Hartnett ME. 2011. The role of RPE cell-associated VEGF in choroidal endothelial cell transmigration across the RPE. Invest Ophthalmol Vis Sci 52(1):570-8. [PubMed: 20811045]  [MGI Ref ID J:171563]

Zelzer E; McLean W; Ng YS; Fukai N; Reginato AM; Lovejoy S; D'Amore PA; Olsen BR. 2002. Skeletal defects in VEGF(120/120) mice reveal multiple roles for VEGF in skeletogenesis. Development 129(8):1893-904. [PubMed: 11934855]  [MGI Ref ID J:75934]

van den Akker NM; Caolo V; Wisse LJ; Peters PP; Poelmann RE; Carmeliet P; Molin DG; Gittenberger-de Groot AC. 2008. Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and Notch signalling. Cardiovasc Res 78(2):366-75. [PubMed: 18093989]  [MGI Ref ID J:161912]

van den Akker NM; Molin DG; Peters PP; Maas S; Wisse LJ; van Brempt R; van Munsteren CJ; Bartelings MM; Poelmann RE; Carmeliet P; Gittenberger-de Groot AC. 2007. Tetralogy of fallot and alterations in vascular endothelial growth factor-A signaling and notch signaling in mouse embryos solely expressing the VEGF120 isoform. Circ Res 100(6):842-9. [PubMed: 17332426]  [MGI Ref ID J:133799]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice may be bred as heterozygotes. Most homozygotes die shortly after birth due to cardiorespiratory distress, survivors die within two weeks of age due to cardiac failure.

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