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

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6J Donor Strain 129S2 via D3 ES cell line Generation N11 (01-JAN-06) Generation Definitions   Donating Investigator Dr. Richard Hynes,   Massachusetts Institute of Technology

Description
Mice homozygous for the Itga5^tm1Hyn targeted mutation die during embryonic development. Homozygous mutant embryos exhibit defects in the vasculature of the yolk sac and the embyro as well as severe defects in posterior and extraembryonic mesoderm. Implantation and initiation of gastrulation and neurulation is normal. There is normal development of notochord, somite and considerable development of brain, optic and otic anlagen and branchial arches.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

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.

Itga5^tm1Hyn/Itga5^tm1Hyn

        involves: 129S2/SvPas * C57BL/6J

• mortality/aging
• complete embryonic lethality during organogenesis
  • homozygotes die between E10.0 and E11.0   (MGI Ref ID J:16248)
• embryogenesis phenotype
• abnormal embryonic tissue morphology   (MGI Ref ID J:16248)
• • abnormal mesoderm development
    • at E9.5, the extraembryonic mesodermal layer is reduced and separated from the extraembryonic endoderm   (MGI Ref ID J:16248)
  • • abnormal paraxial mesoderm morphology
      • at E9.5, homozygotes display a deficit in paraxial mesoderm in the region flanking the neural tube   (MGI Ref ID J:16248)
      • mesenchymeal cells, normally found on the dorsal side of somites are absent   (MGI Ref ID J:16248)
  • failure of somite differentiation
    • at E9.5, mutant embryos lack somites in the truncated posterior regions   (MGI Ref ID J:16248)
    • in contrast, normal somite numbers (7-10 pairs) are noted anteriorly   (MGI Ref ID J:16248)
    • at E8.0-E8.5, most mutant embryos exhibit normal numbers of somites relative to wild-type embryos (4-13 pairs)   (MGI Ref ID J:16248)
  • kinked neural tube
    • at E9.5, homozygotes exhibit kinked neural tubes in the posterior trunk region   (MGI Ref ID J:16248)
• abnormal extraembryonic tissue morphology   (MGI Ref ID J:16248)
• • abnormal vitelline vasculature morphology
    • at E9.5, mutant yolk sacs display abnormal blood vessels, with large numbers of blood cells leaking into the exocoelomic space   (MGI Ref ID J:16248)
• abnormal rostral-caudal axis patterning
  • at E8.5, homozygotes display an abnormal curvature and a slightly truncated anterior-posterior axis   (MGI Ref ID J:16248)
  • at E9.5, the posterior trunk of mutant embryos is deformed and only 1/3 of E9.0 wild-type length   (MGI Ref ID J:16248)
  • although delayed, the anterior region (including heads, branchial arches and heart) appears relatively unaffected   (MGI Ref ID J:16248)
• embryonic growth retardation
  • at E9.5, mutant embryos are developmentally retarded and equivalent in size to E9.0 wild-type embryos   (MGI Ref ID J:16248)
  • by E10.5, mutant embryos are equivalent in size to E9.5 wild-type embryos   (MGI Ref ID J:16248)
• incomplete embryo turning
  • at E9.5, mutant embryos are only partially turned into the fetal position   (MGI Ref ID J:16248)
• growth/size phenotype
• embryonic growth retardation
  • at E9.5, mutant embryos are developmentally retarded and equivalent in size to E9.0 wild-type embryos   (MGI Ref ID J:16248)
  • by E10.5, mutant embryos are equivalent in size to E9.5 wild-type embryos   (MGI Ref ID J:16248)
• nervous system phenotype
• kinked neural tube
  • at E9.5, homozygotes exhibit kinked neural tubes in the posterior trunk region   (MGI Ref ID J:16248)
• cardiovascular system phenotype
• abnormal blood vessel morphology
  • all homozygotes form hearts and a vascular system; however, primitive blood vessels are distended and leaky   (MGI Ref ID J:16248)
  • at E9.5, homozygotes show vascular defects both in the embryo and in extraembryonic vasculature, with fewer blood cells present in the heart and blood vessels   (MGI Ref ID J:16248)
• • abnormal dorsal aorta morphology
    • at E9.5, the mutant dorsal aortae are not fully closed, with leakage of primitive blood cells into the mesoderm-deficient space   (MGI Ref ID J:16248)
  • abnormal vitelline vasculature morphology
    • at E9.5, mutant yolk sacs display abnormal blood vessels, with large numbers of blood cells leaking into the exocoelomic space   (MGI Ref ID J:16248)
• cellular phenotype
• *normal* cellular phenotype
  • mutant embryonic fibroblasts are able to assemble fibronectin matrix, form focal contacts, and migrate on fibronectin   (MGI Ref ID J:16248)

View Research Applications

Research Applications

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

Itga5^tm1Hyn related

Cancer Research
Genes Regulating Growth and Proliferation

Cardiovascular Research
Heart Abnormalities
Vascular Defects

Cell Biology Research
Cell Cycle Regulation
Cell Motility Defects
Defects in Cell Adhesion Molecules
Defects in Extracellular Matrix Molecules

Developmental Biology Research
Cell Motility Defects
Defects in Cell Adhesion Molecules
Embryonic Lethality (Homozygous)
Mesodermal Defects
Neural Crest Defects

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Internal/Organ Research
Heart Abnormalities

Research Tools
Apoptosis Research
Cell Biology Research
Developmental Biology Research
Hematological Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Itga5tm1Hyn
Allele Name		targeted mutation 1, Richard Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		alpha5-; alpha5-null;
Mutation Made By		Dr. 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		Itga5, integrin alpha 5 (fibronectin receptor alpha)
Chromosome		15
Gene Common Name(s)		CD49e; FNRA; Fnra; Itga5_retired; VLA5A; fibronectin receptor alpha (Itga5);
Molecular Note		A neomycin resistance cassette replaced 330 bp of the gene, deleting most of the first exon. [MGI Ref ID J:16248]

Genotyping

Genotyping Information

Genotyping Protocols

Itga5^tm1Hyn, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Yang JT; Rayburn H; Hynes RO. 1993. Embryonic mesodermal defects in alpha 5 integrin-deficient mice. Development 119(4):1093-105. [PubMed: 7508365]  [MGI Ref ID J:16248]

Additional References

Goh KL; Yang JT; Hynes RO. 1997. Mesodermal defects and cranial neural crest apoptosis in alpha5 integrin-null embryos. Development 124(21):4309-19. [PubMed: 9334279]  [MGI Ref ID J:44237]

Itga5^tm1Hyn related

Chan CS; Weeber EJ; Kurup S; Sweatt JD; Davis RL. 2003. Integrin requirement for hippocampal synaptic plasticity and spatial memory. J Neurosci 23(18):7107-16. [PubMed: 12904471]  [MGI Ref ID J:84858]

Goh KL; Yang JT; Hynes RO. 1997. Mesodermal defects and cranial neural crest apoptosis in alpha5 integrin-null embryos. Development 124(21):4309-19. [PubMed: 9334279]  [MGI Ref ID J:44237]

Haack H; Hynes RO. 2001. Integrin receptors are required for cell survival and proliferation during development of the peripheral glial lineage. Dev Biol 233(1):38-55. [PubMed: 11319856]  [MGI Ref ID J:69286]

Li L; Welser-Alves J; van der Flier A; Boroujerdi A; Hynes RO; Milner R. 2012. An angiogenic role for the alpha5beta1 integrin in promoting endothelial cell proliferation during cerebral hypoxia. Exp Neurol 237(1):46-54. [PubMed: 22721769]  [MGI Ref ID J:187182]

Mittal A; Pulina M; Hou SY; Astrof S. 2010. Fibronectin and integrin alpha 5 play essential roles in the development of the cardiac neural crest. Mech Dev 127(9-12):472-84. [PubMed: 20807571]  [MGI Ref ID J:165711]

Pulina MV; Hou SY; Mittal A; Julich D; Whittaker CA; Holley SA; Hynes RO; Astrof S. 2011. Essential roles of fibronectin in the development of the left-right embryonic body plan. Dev Biol 354(2):208-20. [PubMed: 21466802]  [MGI Ref ID J:173656]

Stenzel D; Lundkvist A; Sauvaget D; Busse M; Graupera M; van der Flier A; Wijelath ES; Murray J; Sobel M; Costell M; Takahashi S; Fassler R; Yamaguchi Y; Gutmann DH; Hynes RO; Gerhardt H. 2011. Integrin-dependent and -independent functions of astrocytic fibronectin in retinal angiogenesis. Development 138(20):4451-63. [PubMed: 21880786]  [MGI Ref ID J:178335]

Taverna D; Ullman-Cullere M; Rayburn H; Bronson RT; Hynes RO. 1998. A test of the role of alpha5 integrin/fibronectin interactions in tumorigenesis. Cancer Res 58(4):848-53. [PubMed: 9485045]  [MGI Ref ID J:45769]

Yang JT; Bader BL; Kreidberg JA; Ullman-Cullere M; Trevithick JE; Hynes RO. 1999. Overlapping and independent functions of fibronectin receptor integrins in early mesodermal development. Dev Biol 215(2):264-77. [PubMed: 10545236]  [MGI Ref ID J:58411]

van der Flier A; Badu-Nkansah K; Whittaker CA; Crowley D; Bronson RT; Lacy-Hulbert A; Hynes RO. 2010. Endothelial alpha5 and alphav integrins cooperate in remodeling of the vasculature during development. Development 137(14):2439-49. [PubMed: 20570943]  [MGI Ref ID J:161850]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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