Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N8   Donating Investigator Richard Hynes,   Massachusetts Institute of Technology

Description
The majority (80%) of homozygous null Itgav mice die during embryonic days 9.5-11.5. These mice are characterized by pericardial edema and retarded growth probably due to placental defects. Mice surviving this period die at birth exhibiting intracranial and intestinal hemorrhaging. Angiogenesis in other tissues is normal. Cleft palate is also observed.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes driven by the mouse phosphoglycerate kinase promoter was used to disrupt the Itgav exon 1 and a portion of intron 1. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6J females.

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Itgav^tm1Hyn/Itgav^tm1Hyn

        either: (involves: 129/Sv * 129S2/SvPas) or (involves: 129S2/SvPas * C57BL/6J)

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:50951)
  • about 80% of homozygotes die between E10 and E12
• neonatal lethality (MGI Ref ID J:50951)
  • 20% of homozygous embryos continue development and die within the first day after birth displaying intracranial and intestinal hemorrhage
• embryogenesis phenotype
• abnormal extraembryonic tissue morphology (MGI Ref ID J:50951)
  • seen in 80% of homozygotes which experience embryonic lethality
• abnormal placenta morphology (MGI Ref ID J:50951)
• abnormal placenta labyrinth morphology (MGI Ref ID J:50951)
  • labyrinthine zone of placenta was reduced
• abnormal placenta vasculature (MGI Ref ID J:50951)
  • fewer fetal blood vessels or absence of such vessels
  • allantoic and fetal placental blood sinuses frequently dilated and filled with fetal red blood cells
• abnormal trophoblast layer morphology (MGI Ref ID J:50951)
  • trophoblastic region abnormally thick and compact
• abnormal vitelline vasculature (MGI Ref ID J:50951)
  • yolk sac blood vessels are somewhat distended at E10.5 but otherwise normal
• embryonic growth retardation (MGI Ref ID J:50951)
  • development is normal to E9.5
  • developmental delays start around E10.5 in about 80% of embryos
• small branchial arch (MGI Ref ID J:50951)
  • underdeveloped in 80% of homozygotes at E10.5
• craniofacial phenotype
• abnormal head morphology (MGI Ref ID J:50951)
  • smaller heads at E10.5 in 80% of homozygotes
  • heads appear hydrocephalic in 20% of homozygotes surviving to birth
• cleft palate (MGI Ref ID J:50951)
  • anteroposterior cleft in mice surviving to birth
• abnormal viscerocranium morphology (MGI Ref ID J:50951)
  • smaller nasal processes at E10.5 in 80% of homozygotes
  • malformed secondary palate in 20% of homozygotes
• small branchial arch (MGI Ref ID J:50951)
  • underdeveloped in 80% of homozygotes at E10.5
• cardiovascular system phenotype
• abnormal heart morphology (MGI Ref ID J:50951)
• enlarged heart (MGI Ref ID J:50951)
  • heart becomes increasingly distended after E10.5 in 80% of homozygotes
• pericardial edema (MGI Ref ID J:50951)
  • sometimes develops around E10.5 in homozygotes that die as embryos
• poorly developed ventricular trabeculae (MGI Ref ID J:50951)
  • myocardial trabeculae are less complex
• thin myocardial wall (MGI Ref ID J:50951)
• abnormal vasculature (MGI Ref ID J:50951)
  • less complex primary perineural plexus with distended blood vessels at E10.5 in 80% of homozygotes
  • blood vessels branch deeply into the brain parenchyma, are distended and eventually leak in mice surviving to birth
• hemorrhage (MGI Ref ID J:50951)
• gastrointestinal hemorrhage (MGI Ref ID J:50951)
  • intestinal hemorrhaging in 20% of homozygotes
• intracerebral hemorrhage (MGI Ref ID J:50951)
  • begins around E12.5 in 20% of embryos surviving to birth
  • progressively worsens
  • bleeding first appears in the floor of the telencephalon at the ganglionic eminence
  • by E13.5 more severe bleeding spreads to the diencephalons, cortex of forebrain and cortex of midbrain
• growth/size phenotype
• abnormal embryonic growth/weight/body size (MGI Ref ID J:50951)
• embryonic growth retardation (MGI Ref ID J:50951)
  • development is normal to E9.5
  • developmental delays start around E10.5 in about 80% of embryos
• digestive/alimentary phenotype
• cleft palate (MGI Ref ID J:50951)
  • anteroposterior cleft in mice surviving to birth
• gastrointestinal hemorrhage (MGI Ref ID J:50951)
  • intestinal hemorrhaging in 20% of homozygotes
• nervous system phenotype
• intracerebral hemorrhage (MGI Ref ID J:50951)
  • begins around E12.5 in 20% of embryos surviving to birth
  • progressively worsens
  • bleeding first appears in the floor of the telencephalon at the ganglionic eminence
  • by E13.5 more severe bleeding spreads to the diencephalons, cortex of forebrain and cortex of midbrain
• muscle phenotype
• poorly developed ventricular trabeculae (MGI Ref ID J:50951)
  • myocardial trabeculae are less complex
• thin myocardial wall (MGI Ref ID J:50951)
• skeleton phenotype
• abnormal viscerocranium morphology (MGI Ref ID J:50951)
  • smaller nasal processes at E10.5 in 80% of homozygotes
  • malformed secondary palate in 20% of homozygotes
• homeostasis/metabolism phenotype
• pericardial edema (MGI Ref ID J:50951)
  • sometimes develops around E10.5 in homozygotes that die as embryos

Itgav^tm1Hyn/Itgav^tm1Hyn

        involves: 129S2/SvPas * C57BL/6 * FVB/N

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:79611)
  • about 80% of homozygotes die between E10 and E12
• neonatal lethality (MGI Ref ID J:79611)
  • 20% of homozygous embryos continue development and die within the first day after birth
• cardiovascular system phenotype
• abnormal vasculature (MGI Ref ID J:79611)
  • space develops between blood vessels and neural tissue of the brain
• intracerebral hemorrhage (MGI Ref ID J:79611)
• nervous system phenotype
• intracerebral hemorrhage (MGI Ref ID J:79611)

View Research Applications

Research Applications

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

Developmental Biology Research
Defects in Cell Adhesion Molecules
Embryonic Lethality (Homozygous) (incomplete)
Internal/Organ Defects (vasculature)
Neurodevelopmental Defects
Perinatal Lethality (Homozygous)

Itgav^tm1Hyn related

Cardiovascular Research
Vascular Defects

Developmental Biology Research
Neurodevelopmental Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Itgavtm1Hyn
Allele Name		targeted mutation 1, Richard Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		alphav-null;
Mutation Made By		Richard Hynes,   Massachusetts Institute of Technology
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Itgav, integrin alpha V
Chromosome		2
Gene Common Name(s)		1110004F14Rik; 2610028E01Rik; CD51; D430040G12Rik; DKFZp686A08142; MSK8; RIKEN cDNA 1110004F14 gene; RIKEN cDNA 2610028E01 gene; RIKEN cDNA D430040G12 gene; VNRA; alphav-integrin; vitronectin receptor alpha polypeptide (VNRA);
Molecular Note		A neomycin resistance cassette replaced a genomic fragment containing the first exon, which encodes the signal peptide and first 30 amino acids of the mature protein. No mature protein was detected by immunoprecipitation studies on the cell surface of E16 or neonate dermal fibroblasts derived from homozygous mice. [MGI Ref ID J:50951]

Genotyping

Genotyping Information

Genotyping Protocols

Itgav^tm1Hyn, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Bader BL; Rayburn H; Crowley D; Hynes RO. 1998. Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins. Cell 95(4):507-19. [PubMed: 9827803]  [MGI Ref ID J:50951]

Additional References

Itgav^tm1Hyn related

Lacy-Hulbert A; Smith AM; Tissire H; Barry M; Crowley D; Bronson RT; Roes JT; Savill JS; Hynes RO. 2007. Ulcerative colitis and autoimmunity induced by loss of myeloid alphav integrins. Proc Natl Acad Sci U S A 104(40):15823-8. [PubMed: 17895374]  [MGI Ref ID J:125508]

McCarty JH; Monahan-Earley RA; Brown LF; Keller M; Gerhardt H; Rubin K; Shani M; Dvorak HF; Wolburg H; Bader BL; Dvorak AM; Hynes RO. 2002. Defective associations between blood vessels and brain parenchyma lead to cerebral hemorrhage in mice lacking alphav integrins. Mol Cell Biol 22(21):7667-77. [PubMed: 12370313]  [MGI Ref ID J:79611]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129S2 background and has been backcrossed to C57BL/6J for at least seven generations. The donating investigator maintains this strain using heterozygous intercrosses, avoiding brother-sister matings.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

General Terms and Conditions

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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