Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation F?+1N1p   Donating Investigator David Ginsburg,   University of Michigan

Description
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) was immunodetected. Serum from mutant mice has no plasma plasminogen activator inhibitor 1 (PAI-1) binding capacity and can not support cell spreading on tissue culture plastic surface. Thrombosis rate after arterial injury is enhanced and angiogenesis in response to tissue injury is decreased in mutant mice. This mutant mouse strain represents a model that may be useful in studies of the in vivo function of vitronectin.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt all of the coding sequence of the targeted gene and approximately 3 kb of downstream sequence. 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 mice were crossed to B6D2F1/J female mice, and then backcrossed to C57BL/6J for 12 generations before being made homozygous.

Control Information

	Control
	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

Vtn^tm1Dgi/Vtn^tm1Dgi

        B6.129S2-Vtn^tm1Dgi

• homeostasis/metabolism phenotype
• abnormal blood coagulation (MGI Ref ID J:134443)
  • in a model of ferric chloride induced vessel injury, mutants exhibit unstable thrombi and a greater number of emboli
  • in a cremaster muscle arteriole mode where vessel injury is induced by a nitrogen dye laser, mutants exhibit fewer platelets, lower fibrin content, and unstable fibrin within the thrombi compared to wild-type
• abnormal platelet physiology (MGI Ref ID J:134443)
  • early platelet adhesion is not affected, however the second wave of thrombin-induced aggregation of gel-filtered platelets is abolished at a low concentration of thrombin
  • mutant platelet-rich plasma shows a 32% increase in adenosine diphosphate-induced platelet aggregation in vitro compared to wild-type
  • whole blood of mutants exhibits an increase in shear-induced platelet aggregation
• abnormal response to injury (MGI Ref ID J:134443)
  • in a model of ferric chloride induced vessel injury, mutants exhibit unstable thrombi and a greater number of emboli
  • vessel occlusion is delayed and frequent vessel re-opening occurs in mutants where vessel injury was induced with ferric chloride
  • in a cremaster muscle arteriole mode where vessel injury is induced by a nitrogen dye laser, mutants exhibit fewer platelets, lower fibrin content, and unstable fibrin within the thrombi compared to wild-type
• hematopoietic system phenotype
• abnormal platelet physiology (MGI Ref ID J:134443)
  • early platelet adhesion is not affected, however the second wave of thrombin-induced aggregation of gel-filtered platelets is abolished at a low concentration of thrombin
  • mutant platelet-rich plasma shows a 32% increase in adenosine diphosphate-induced platelet aggregation in vitro compared to wild-type
  • whole blood of mutants exhibits an increase in shear-induced platelet aggregation

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

Vtn^tm1Dgi/Vtn^tm1Dgi

        involves: 129S2/SvPas * C57BL/6 * DBA/2J

• normal phenotype
• no abnormal phenotype detected (MGI Ref ID J:30296)
  • viable and fertile with no differences in blood counts or autopsy findings; histological analysis did not detect any abnormalities in the nervous system, heart, lung, liver and kidney

View Research Applications

Research Applications

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

Vtn^tm1Dgi related

Cardiovascular Research
Vascular Defects (Thrombosis)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Vtntm1Dgi
Allele Name		targeted mutation 1, David Ginsburg
Allele Type		Targeted (knock-out)
Common Name(s)		VN-;
Mutation Made By		XianXian Zheng,   University of Michigan
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Vtn, vitronectin
Chromosome		11
Gene Common Name(s)		AI256434; Aa1018; MGC124961; V75; VN; VNT; expressed sequence AI256434;
Molecular Note		A PGK-neomycin cassette replaced all eight exons. Western blot analysis did not detect protein in plasma of homozygous mutant mice, and cell adhesion experiments with sera derived from homozygous mice demonstrated that serum spreading activity was absent. [MGI Ref ID J:30296]

Genotyping

Genotyping Information

Genotyping Protocols

Vtn^tm1Dgi, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Zheng X; Saunders TL; Camper SA; Samuelson LC; Ginsburg D. 1995. Vitronectin is not essential for normal mammalian development and fertility. Proc Natl Acad Sci U S A 92(26):12426-30. [PubMed: 8618914]  [MGI Ref ID J:30296]

Additional References

Fay WP; Parker AC; Ansari MN; Zheng X; Ginsburg D. 1999. Vitronectin inhibits the thrombotic response to arterial injury in mice. Blood 93(6):1825-30. [PubMed: 10068653]  [MGI Ref ID J:53442]

Liaw L; Birk DE; Ballas CB; Whitsitt JS; Davidson JM; Hogan BL. 1998. Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest 101(7):1468-78. [PubMed: 9525990]  [MGI Ref ID J:46863]

Vtn^tm1Dgi related

Akerman ME; Pilch J; Peters D; Ruoslahti E. 2005. Angiostatic peptides use plasma fibronectin to home to angiogenic vasculature. Proc Natl Acad Sci U S A 102(6):2040-5. [PubMed: 15687502]  [MGI Ref ID J:96503]

Koschnick S; Konstantinides S; Schafer K; Crain K; Loskutoff DJ. 2005. Thrombotic phenotype of mice with a combined deficiency in plasminogen activator inhibitor 1 and vitronectin. J Thromb Haemost 3(10):2290-5. [PubMed: 16194205]  [MGI Ref ID J:114352]

Lazar MH; Christensen PJ; Du M; Yu B; Subbotina NM; Hanson KE; Hansen JM; White ES; Simon RH; Sisson TH. 2004. Plasminogen activator inhibitor-1 impairs alveolar epithelial repair by binding to vitronectin. Am J Respir Cell Mol Biol 31(6):672-8. [PubMed: 15308506]  [MGI Ref ID J:104660]

Reheman A; Gross P; Yang H; Chen P; Allen D; Leytin V; Freedman J; Ni H. 2005. Vitronectin stabilizes thrombi and vessel occlusion but plays a dual role in platelet aggregation. J Thromb Haemost 3(5):875-83. [PubMed: 15733060]  [MGI Ref ID J:134443]

Wei C; Moller CC; Altintas MM; Li J; Schwarz K; Zacchigna S; Xie L; Henger A; Schmid H; Rastaldi MP; Cowan P; Kretzler M; Parrilla R; Bendayan M; Gupta V; Nikolic B; Kalluri R; Carmeliet P; Mundel P; Reiser J. 2008. Modification of kidney barrier function by the urokinase receptor. Nat Med 14(1):55-63. [PubMed: 18084301]  [MGI Ref ID J:130835]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129 background, was crossed once to B6D2F1/J before being backcrossed for 12 generations on the C57BL/6J background and is maintained as a homozygote.

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

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. 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
	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

      Purchasing Information
      JAX^® Mice Orders
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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.

No Liability

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.