Overview

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.

Donating Investigator

Patricia D'Amore, Schepens Eye Research Institute

Genetic overview

Genetic Background	Generation

Vegfa^tm1Pec

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Vegfa	vascular endothelial growth factor A

View Genetics

Research Applications

Cardiovascular Research
Sensorineural Research
Developmental Biology Research

View All Research Applications

Details

Detailed 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 Suggestions

Approximate Controls

Wild-type from the colony
101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

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):495-502PubMed: 10229225 MGI: J:56003

View All References

Genetics

Vegfa^tm1Pec

Allele Symbol: Vegfa^tm1Pec

Allele Name	targeted mutation 1, Peter Carmeliet
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	VEGF¹²⁰
Gene Symbol and Name	Vegfa, vascular endothelial growth factor A
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	17
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.
Mutations Made By	Dr. Peter Carmeliet, University of Leuven

Disease/Phenotype

Disease Terms

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

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

newborn respiratory distress syndrome

Research Areas By Phenotype

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

Cardiovascular Research
- Vascular Defects
Sensorineural Research
- Eye Defects
Developmental Biology Research
- Eye Defects
- Internal/Organ Defects
  - vasculature

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Vegfa^tm1Pec/Vegfa^tm1Pec
involves: 129S1/Sv * 129X1/SvJ

behavior/neurological phenotype

lethargy
- become progressively lethargic

cellular phenotype

abnormal vascular regression
- exhibit signs of regression in vessels of the pharyngeal arch that should normally persist

increased neuron apoptosis
- of gonadotropin-releasing hormone neurons

abnormal neuronal migration
- caudally migrating somata of facial branchiomotor neurons prematurely turns dorsally and dives through the basal plate in ectopic anterior locations

craniofacial phenotype

abnormal fourth pharyngeal 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

abnormal pharyngeal arch artery morphology
- E14.5 embryos and neonates have remodeling defects of the 4th, 6th and, less frequently, 3rd pharyngeal arch arteries
- 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

short mandible

abnormal coronal suture morphology
- cranial sutures between the frontal and parietal bones fail to close properly

abnormal mandible morphology
- vascular density in the mandible is significantly reduced and the vessels are abnormally dilated and tortuous

abnormal third pharyngeal arch artery morphology

absent incisors
- 43% lack incisors

cleft palate
- seen in 74% of mutants

abnormal sixth pharyngeal 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

digestive/alimentary phenotype

cleft palate
- seen in 74% of mutants

embryo phenotype

abnormal pharyngeal arch artery morphology
- E14.5 embryos and neonates have remodeling defects of the 4th, 6th and, less frequently, 3rd pharyngeal arch arteries
- 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

abnormal fourth pharyngeal 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

abnormal third pharyngeal arch artery morphology

abnormal sixth pharyngeal 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

endocrine/exocrine gland phenotype

ectopic thymus
- 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus

abnormal thymus morphology
- vessel density and total vascular volume are reduced in the thymus

thymus hypoplasia
- 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus

absent parathyroid glands
- absent in 4 of 12 neonates, and when present, they are associated with an ectopic thymic lobe

athymia
- 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus

growth/size/body region phenotype

cleft palate
- seen in 74% of mutants

decreased body weight
- neonates surviving the perinatal period have normal body weights at birth but fail to gain weight

enlarged heart

absent incisors
- 43% lack incisors

hematopoietic system phenotype

decreased lymphocyte cell number
- fraction of circulating lymphocytes is decreased

thymus hypoplasia
- 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus

athymia
- 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus

ectopic thymus
- 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus

abnormal thymus morphology
- vessel density and total vascular volume are reduced in the thymus

homeostasis/metabolism phenotype

increased circulating creatinine level
- at P6, plasma creatinine levels are significantly higher than those in wild-type controls

cyanosis
- homozyogotes that die in the perinatal period become cyanotic immediately after birth

increased blood urea nitrogen level
- at P6, plasma urea levels are significantly higher than those in wild-type controls

immune system phenotype

athymia
- 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus

abnormal thymus morphology
- vessel density and total vascular volume are reduced in the thymus

ectopic thymus
- 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus

decreased lymphocyte cell number
- fraction of circulating lymphocytes is decreased

thymus hypoplasia
- 5 of 12 mutants either have a hypoplastic, absent, or ectopically located thymus

mortality/aging

neonatal lethality, incomplete penetrance
- neonates die shortly after birth because of cardio-respiratory distress
- about half die within a few hours of birth because of bleeding in several organs

postnatal lethality, complete penetrance
- 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)

muscle phenotype

abnormal sarcomere morphology
- sarcomere rarefication

abnormal myocardial fiber morphology
- dria, and increased levels of fetal genes that are re-introduced during the course of ischemic heart disease
- 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

decreased cardiac muscle contractility
- depressed left ventricular contractility; enlarged systolic left ventricular and diastolic left ventricular diameters, impaired fractional shortening, and reduced aortic outflow velocity
- suffer severe left ventricular pump failure and show signs of right ventricular failure, including accumulation of ascitic fluid and increased liver-to-body weight
- exhibit dysmorphic, weak heart contractions

enlarged myocardial fiber
- cardiomyoctes are slightly larger at P12

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

abnormal cardiac muscle relaxation
- depressed left ventricular relaxation

nervous system phenotype

increased neuron apoptosis
- of gonadotropin-releasing hormone neurons

abnormal neuronal migration
- caudally migrating somata of facial branchiomotor neurons prematurely turns dorsally and dives through the basal plate in ectopic anterior locations

decreased neuron number
- reduced gonadotropin-releasing hormone neurons at E14.5, E15.5 and E18.5

abnormal facial motor nucleus morphology
- facial motor nuclei appear elongated or dumbbell-shaped
- in 7 of 9 mutants, one or both facial motor nuclei are shifted anteriorly, however facial nerve is not defasciculated

renal/urinary system phenotype

abnormal kidney arterial blood vessel morphology
- at P0.5 and P3, the number of renin-expressing branch points per kidney section is reduced relative to that in wild-type kidneys
- although lobar arteries develop normally, further branching into arcuate, interlobular, and afferent/efferent arterioles progressively
- fewer SMA-stained kidney arteries are detected at all postnatal ages relative to wild-type controls

abnormal glomerular capillary endothelium morphology
- by P6, ~40% fewer glomeruli contain CD34-positive endothelial cells; however, endothelial fenestration occurs as in wild-type controls
- endothelial cells appear to detach from their underlying basement membrane and show signs of cellular degeneration and death (blebbing, vacuolization, nuclear disintegration)
- at E15.5 to P6, fewer glomeruli are vascularized, as revealed by CD34-staining

abnormal nephrogenic zone morphology
- at P3, the nephrogenic cortex is reduced by ~25% relative to that in wild-type kidneys

abnormal peritubular capillary morphology
- at P6, the distance between neighboring peritubular capillaries is enlarged, suggesting kidney ischemia
- 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
- by P6, peritubular capillaries remain dilated, appear tortuous and irregular, and lack symmetric patterning

abnormal kidney efferent arteriole morphology
- by P6, the number of efferent arterioles is reduced to ~50% of that in wild-type kidneys

abnormal renal glomerulus basement membrane morphology
- at P0.5, the GBM often displays a variable shape and thickness, and appears more irregular and tortuous

decreased renal glomerular filtration rate
- at P6, glomerular filtration is impaired, as shown by elevated levels of plasma creatinine and urea
- pe kidneys
- GFR cannot be determined by measuring creatinine clearance, as mutant neonates are fragile
- 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

decreased renal glomerulus number
- at P0.5, P3, and P6, homozygotes display ~25% fewer glomeruli/kidney section relative to wild-type controls
- Normal - however, glomerular density (i.e., glomeruli per mm2) is not reduced because kidneys are smaller

abnormal proximal convoluted tubule morphology
- at P0.5, P3, and P6, fewer proximal convoluted tubules are observed relative to wild-type controls
- ultrastructural signs of ischemia are detected in the proximal tubules, unlike in wild-type kidneys
- Normal - in contrast, distal convoluted tubules are of normal size, number and morphology

abnormal renal glomerulus basement membrane thickness
- the GBM often displays a variable thickness in mature glomeruli after E17.5

expanded mesangial matrix
- excessive matrix deposition is already detectable in fetal mature glomeruli after E17.5
- most sclerotic glomeruli accumulate an unusual amount of collagen type IV, fibrin, fibronectin, and laminin

renal glomerulus hypertrophy
- by P6, mutant sclerotic glomeruli are ~3-fold larger than mature wild-type glomeruli

small kidney
- 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
- at P0.5, P3, and P6, mutant kidneys are smaller than wild-type

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
- Normal - however, parietal epithelial cells in the capsule of Bowman and podocytes remain normal in most glomeruli and persist even when glomeruli become sclerotic
- in sclerotic glomeruli, the entire capillary bed often disappears and is replaced by amorphous granular necrotic debris
- at P6, abnormal accumulation of laminin is noted in mutant sclerotic glomeruli but not in mature wild-type glomeruli

renal ischemia
- at P6, the distance between neighboring peritubular capillaries is enlarged, suggesting kidney 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
- pe kidneys

abnormal kidney afferent arteriole morphology
- by P6, the number of afferent arterioles is reduced to ~50% of that in wild-type kidneys

abnormal mesangial cell morphology
- mesangial cells gradually disappear as glomeruli become sclerotic and loose their capillary network

abnormal kidney interlobular artery morphology
- by P6, the number of interlobular arteries is reduced to one-third of that in wild-type kidneys

abnormal loop of Henle morphology
- at P6, fewer but often enlarged and tortuous loops of Henle are observed, unlike in wild-type kidneys
- ultrastructural signs of ischemia are detected in the loops of Henle, unlike in wild-type kidneys

decreased glomerular capillary number
- when capillary loops form, they fail to expand into a complex tuft and eventually disintegrate
- at E15.5 to P6, the number of laminin-positive capillary loops per glomerulus is reduced relative to that in wild-type controls

dilated proximal convoluted tubules
- at P3 and P6, proximal convoluted tubules appear enlarged relative to those in wild-type kidneys

pale kidney
- mutant kidneys are generally paler than wild-type

abnormal glomerular capillary morphology
- at P0.5, mutant glomeruli exhibit fewer and disordered capillary loops, unlike wild-type glomeruli

abnormal kidney blood vessel morphology
- capillary growth in renal glomeruli is retarded
- fewer renal arteries

cardiovascular system phenotype

abnormal arteriole morphology
- fewer and smaller arterioles in the retina
- less than half of the number of arterioles grow out over only 35% of the retina and 53% of the vascular bed

abnormal capillary morphology
- capillaries in hearts are irregular, tortuous and slightly dilated, indicative of incomplete vessel remodeling
- capillary density and size in the septum are less affected in those mice that die 2 weeks after birth (rather than perinatally)
- defective capillary vessel formation results in larger inter-capillary distances in hearts and an increase in myocyte-to-capillary ratios at P12
- exhibit more numerous, dilated and fragile capillaries in the central retina

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

abnormal fourth pharyngeal 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

abnormal kidney blood vessel morphology
- fewer renal arteries
- capillary growth in renal glomeruli is retarded

abnormal kidney interlobular artery morphology
- by P6, the number of interlobular arteries is reduced to one-third of that in wild-type kidneys

abnormal peritubular capillary morphology
- by P6, peritubular capillaries remain dilated, appear tortuous and irregular, and lack symmetric patterning
- 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
- at P6, the distance between neighboring peritubular capillaries is enlarged, suggesting kidney ischemia

abnormal retinal vasculature morphology
- exhibit more numerous and dilated capillaries in the central retina
- fewer periendothelial cells surround the arterioles, venules, and capillaries
- the capillary bed covers the retina only over 2/3 in the small fraction of mice that survive to P9
- outgrowth of capillaries and pericyte coverage is impaired in the retinal vasculature, which remains more immaturely remodeled
- periendothelial cell (PEC) recruitment is delayed, with only scattered PECs detected in and around the optic disc
- only a primitive vascular labyrinth of capillary-like vessels with uniform size develop by P5

prolonged QT interval

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

abnormal cardiovascular system physiology

abnormal glomerular capillary endothelium morphology
- by P6, ~40% fewer glomeruli contain CD34-positive endothelial cells; however, endothelial fenestration occurs as in wild-type controls
- endothelial cells appear to detach from their underlying basement membrane and show signs of cellular degeneration and death (blebbing, vacuolization, nuclear disintegration)
- at E15.5 to P6, fewer glomeruli are vascularized, as revealed by CD34-staining

abnormal ST segment
- exhibit ST-segment depressions in mice at rest
- rapidly develop considerable ST-segment elevations when ventilation is stopped

abnormal third pharyngeal arch artery morphology

abnormal venule morphology
- 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
- fewer and smaller venules in the retina

abnormal cardiac muscle relaxation
- depressed left ventricular relaxation

abnormal kidney efferent arteriole morphology
- by P6, the number of efferent arterioles is reduced to ~50% of that in wild-type kidneys

decreased capillary density
- do not observe a change in capillary density from birth to P12 as in wild-type, indicating a 400% reduction in density
- capillary densities in skeletal muscles are also decreased

increased capillary tortuosity
- capillaries in hearts are irregular, tortuous and slightly dilated, indicative of incomplete vessel remodeling

retinal hemorrhage
- fragile capillaries in the retina cause hemorrhages

cervical aortic arch
- the type-B interruption is associated with persistence of the ductus caroticus, resulting in a cervical aortic arch

right aortic arch
- malformations of the 4th arch artery include a right-sided aortic arch

ventricular septal defect
- ventricular septal defect

abnormal artery morphology
- fewer renal arteries

abnormal blood 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
- about 50% of neonates exhibit severe DiGeorge syndrome-like vessel malformations

abnormal coronary artery morphology
- fewer coronary arteries
- hearts contain fewer coronary vessels, which show less smooth muscle alpha-actin staining

abnormal glomerular capillary morphology
- at P0.5, mutant glomeruli exhibit fewer and disordered capillary loops, unlike wild-type glomeruli

abnormal kidney arterial blood vessel morphology
- fewer SMA-stained kidney arteries are detected at all postnatal ages relative to wild-type controls
- although lobar arteries develop normally, further branching into arcuate, interlobular, and afferent/efferent arterioles progressively
- at P0.5 and P3, the number of renin-expressing branch points per kidney section is reduced relative to that in wild-type kidneys

abnormal myocardial fiber morphology
- dria, and increased levels of fetal genes that are re-introduced during the course of ischemic heart disease
- 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

abnormal T wave
- exhibit T-wave inversions in mice at rest

aorta pulmonary collateral arteries
- observe aortico-pulmonary collateral arteries

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

double aortic arch
- malformations of the 4th arch artery include a double aortic arch

hemorrhage
- about half die within a few hours of birth because of bleeding in several organs

overriding aortic valve

abnormal impulse conducting system conduction
- electrical pulse shows signs of dispersion and heterogeneity

decreased angiogenesis
- capillary and coronary angiogenesis is impaired in the right ventricle and in the atria
- defects most profound in the subendomyocardium

decreased left ventricle systolic pressure
- left ventricular pressure is further reduced during periods of spontaneous arrhythmia

dilated capillary
- slightly dilated in the heart
- in the retina

irregular heartbeat

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

persistent right dorsal aorta
- about 10% of embryos exhibit a dominant right dorsal aorta

abnormal carotid artery morphology
- malformations of the 3rd arch artery result in a double left or right carotid artery

abnormal heart morphology
- 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

decreased cardiac muscle contractility
- depressed left ventricular contractility; enlarged systolic left ventricular and diastolic left ventricular diameters, impaired fractional shortening, and reduced aortic outflow velocity
- suffer severe left ventricular pump failure and show signs of right ventricular failure, including accumulation of ascitic fluid and increased liver-to-body weight
- exhibit dysmorphic, weak heart contractions

decreased glomerular capillary number
- when capillary loops form, they fail to expand into a complex tuft and eventually disintegrate
- at E15.5 to P6, the number of laminin-positive capillary loops per glomerulus is reduced relative to that in wild-type controls

decreased heart rate
- slower heart rates in conscious P6 mice

enlarged heart

abnormal pericyte morphology
- fewer pericytes are detected around peritubular capillaries relative to wild-type kidneys

persistent ductus caroticus
- persistence of the cartoid duct segment between the left carotid and subclavian artery
- the type-B interruption is associated with persistence of the ductus caroticus, resulting in a cervical aortic arch

persistent truncus arteriosis

abnormal kidney afferent arteriole morphology
- by P6, the number of afferent arterioles is reduced to ~50% of that in wild-type kidneys

abnormal pharyngeal arch artery morphology
- E14.5 embryos and neonates have remodeling defects of the 4th, 6th and, less frequently, 3rd pharyngeal arch arteries
- 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

abnormal sixth pharyngeal 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

abnormal vascular regression
- exhibit signs of regression in vessels of the pharyngeal arch that should normally persist

enlarged myocardial fiber
- cardiomyoctes are slightly larger at P12

interrupted aortic arch
- malformations of the 4th arch artery include type-B left 4th aortic arch interruption

prolonged QRS complex duration
- prolonged QRS interval at P6

pulmonary trunk hypoplasia
- hypoplasia of the pulmonary trunk in E13.5-14.5 embryos

respiratory system phenotype

respiratory distress
- a fraction of newborn homozygotes die of respiratory distress syndrome

thick pulmonary interalveolar septum
- a fraction of newborn homozygotes that die of respiratory distress syndrome display a significantly increased alveolar septal thickness at birth

atelectasis
- in a fraction of newborn homozygotes, lung aeration (percentage of total surface filled with air) fails to increase after birth

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

aorta pulmonary collateral arteries
- observe aortico-pulmonary collateral arteries

skeleton phenotype

abnormal mandible morphology
- vascular density in the mandible is significantly reduced and the vessels are abnormally dilated and tortuous

abnormal coronal suture morphology
- cranial sutures between the frontal and parietal bones fail to close properly

absent incisors
- 43% lack incisors

short mandible

vision/eye phenotype

abnormal retinal vasculature morphology
- exhibit more numerous and dilated capillaries in the central retina
- fewer periendothelial cells surround the arterioles, venules, and capillaries
- only a primitive vascular labyrinth of capillary-like vessels with uniform size develop by P5
- periendothelial cell (PEC) recruitment is delayed, with only scattered PECs detected in and around the optic disc
- outgrowth of capillaries and pericyte coverage is impaired in the retinal vasculature, which remains more immaturely remodeled
- the capillary bed covers the retina only over 2/3 in the small fraction of mice that survive to P9

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

retinal hemorrhage
- fragile capillaries in the retina cause hemorrhages

References

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):495-502PubMed: 10229225 MGI: J:56003

Additional - Vegfa^tm1Pec related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Vegfa
- Genotyping resources and troubleshooting
Breeding Considerations

When 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.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129-Vegfa^tm1Pec/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34407 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Vegfatm1Pec

Allele Symbol: Vegfatm1Pec

Disease Terms

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).

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Vegfatm1Pec/Vegfatm1Pecinvolves: 129S1/Sv * 129X1/SvJ

behavior/neurological phenotype

cellular phenotype

craniofacial phenotype

digestive/alimentary phenotype

embryo phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mortality/aging

muscle phenotype

nervous system phenotype

renal/urinary system phenotype

cardiovascular system phenotype

respiratory system phenotype

skeleton phenotype

vision/eye phenotype

References

Additional - Vegfatm1Pec related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Vegfa^tm1Pec

Allele Symbol: Vegfa^tm1Pec

Genotype: Vegfa^tm1Pec/Vegfa^tm1Pec
involves: 129S1/Sv * 129X1/SvJ

Additional - Vegfa^tm1Pec related