Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S2 via D3 ES cell line Generation N19p   Donating Investigator Richard Hynes,   Massachusetts Institute of Technology

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Itga4^tm1Hyn targeted mutation die during embryonic development. Homozygous mutant embryos fail to fuse the allantois with the chorion during placentation. There is a defect in the epicardium and coronary vessels results in in utero cardiac hemorrhage; also known as CD49D, VLA-4.

Development
The Itga4-deficient strain was developed in the lab of Dr. Richard O. Hynes at the Center for Cancer Research at the Massachusetts Institute of Technology.

Control Information

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

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.

Itga4^tm1Hyn/Itga4^tm1Hyn

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

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:23140)
  • about 50% die at around E11 with failure of allantois-chorion fusion
  • about 50% die around E12.5 with cardiac defects, although a few survive up to E14.5
• embryogenesis phenotype
• abnormal extraembryonic tissue morphology (MGI Ref ID J:23140)
  • about half of the embryos exhibit allantois defects between E9.5 and E11.5
• abnormal placenta morphology (MGI Ref ID J:23140)
  • placenta lacks the allantoic component at E9.5 and as a result, the placenta does not form a connection with the embryo
• abnormal chorioallantoic fusion (MGI Ref ID J:23140)
  • failure of fusion of the allantois with the chorion
• dilated allantois (MGI Ref ID J:23140)
  • allantois has an abnormal balloon shape
• cardiovascular system phenotype
• abnormal cardiovascular system morphology (MGI Ref ID J:23140)
  • the 50% of embryos that survive past E11.5 develop cardiac abnormalities between E11.5 and E14.5 but do not have allantois defects
• abnormal coronary artery morphology (MGI Ref ID J:23140)
  • coronary vessels at the atrioventricular sulcus region are absent
• abnormal epicardium morphology (MGI Ref ID J:23140)
  • epicardium is missing on the entire ventricular surface and on part of the atrial surface at E11.5, but not at E10.5
• hemorrhage (MGI Ref ID J:23140)
  • cardiac hemorrhage
• craniofacial phenotype
• abnormal craniofacial morphology (MGI Ref ID J:23140)
  • embryos with cardiac defects exhibit abnormalities in the cranial and facial structures

View Research Applications

Research Applications

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

Itga4^tm1Hyn related

Cardiovascular Research
Heart Abnormalities
Vascular Defects

Cell Biology Research
Cell Motility Defects
Defects in Cell Adhesion Molecules

Developmental Biology Research
Cell Motility Defects
Defects in Cell Adhesion Molecules
Defects in Extracellular Matrix Molecules
Embryonic Lethality (Homozygous)
Internal/Organ Defects (heart)
Neural Crest Defects

Hematological Research
Hematopoietic Defects
Immunological Defects

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency (B cell deficiency)
Immunodeficiency Associated with Other Defects
Inflammation
Lymphoid Tissue Defects

Internal/Organ Research
Heart Abnormalities
X Placental Development

Research Tools
Cell Biology Research
Developmental Biology Research
Immunology and Inflammation Research
Neurobiology Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Itga4tm1Hyn
Allele Name		targeted mutation 1, Richard Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		alpha4-null; alpha4KO;
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		Itga4, integrin alpha 4
Chromosome		2
Gene Common Name(s)		CD49D; IA4; MGC90518; VLA-4 receptor, alpha 4 subunit;
Molecular Note		A neomycin resistance cassette replaced a 950 bp fragment which contained most of the first exon of the gene. [MGI Ref ID J:23140]

Genotyping

Genotyping Information

Genotyping Protocols

Itga4^tm1Hyn, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Yang JT; Rayburn H; Hynes RO. 1995. Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development. Development 121(2):549-60. [PubMed: 7539359]  [MGI Ref ID J:23140]

Additional References

Yang JT; Rando TA; Mohler WA; Rayburn H; Blau HM; Hynes RO. 1996. Genetic analysis of alpha 4 integrin functions in the development of mouse skeletal muscle. J Cell Biol 135(3):829-35. [PubMed: 8909554]  [MGI Ref ID J:36475]

Itga4^tm1Hyn related

Arroyo AG; Yang JT; Rayburn H; Hynes RO. 1999. Alpha4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo. Immunity 11(5):555-66. [PubMed: 10591181]  [MGI Ref ID J:58741]

Grazioli A; Alves CS; Konstantopoulos K; Yang JT. 2006. Defective blood vessel development and pericyte/pvSMC distribution in alpha4 integrin-deficient mouse embryos. Dev Biol 293(1):165-77. [PubMed: 16529735]  [MGI Ref ID J:108464]

Gribi R; Hook L; Ure J; Medvinsky A. 2006. The differentiation program of embryonic definitive hematopoietic stem cells is largely alpha4 integrin independent. Blood 108(2):501-9. [PubMed: 16551970]  [MGI Ref ID J:135680]

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]

Sengbusch JK; He W; Pinco KA; Yang JT. 2002. Dual functions of [alpha]4[beta]1 integrin in epicardial development: initial migration and long-term attachment. J Cell Biol 157(5):873-82. [PubMed: 12021259]  [MGI Ref ID J:76747]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The strain is currently begin maintained by heterozygous matings. Heterozygotes are good breeders. Progeny require testing to determine genotype. The strain was generated on a mixed 129/Sv x C57BL/6 background and is now on both C57BL/6 and 129/Sv backgrounds. Expected coat color from breeding:Black
Diet Information	LabDiet® 5K52/5K67

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.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.