Description

Strain Information

Type Congenic; Gene Trap; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N10F1N1PF5 (30-APR-08)   Donating Investigator John Frangos,   La Jolla Bioengineering Institute

Description
Mice that are homozygous for the gene-trapped allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by immunofluorescence in aorta endothelium from homozygotes, and endothelial nitric oxide synthase isoform (eNOS) is not detected in cell to cell junctions between aorta endothelial cells in these mice. Isolated skeletal muscle arterioles from homozygous mutant mice exhibit reduced vessel dilation and no significant change in wall shear stress responses when intraluminar flow is increased. This mutant mouse strain may be useful in studies of cellular adhesion, vascular integrity and physiology.

Development
A gene trap construct was electroporated into 129S5/SvEvBrd derived Lex-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6-Tyr^c-Brd/c-Brd blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice and distributed on a mixed B6;129S background (Stock No. 003702). In 2006, Dr. John A. Frangos at the La Jolla Bioengineering Institute sent mutant mice derived from backcrossing Stock No. 003702 to C57BL/6J for 6 generations back to The Jackson Laboratory.

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

Pecam1^{Gt(VICTR20)12Lex}/Pecam1^{Gt(VICTR20)12Lex}

        B6.129S5-Pecam1^{Gt(VICTR20)12Lex}

• cardiovascular system phenotype
• decreased vasodilation (MGI Ref ID J:104082)
  • flow mediated dilation of the coronary artery is reduced compared to in wild-type mice
  • a slightly greater proportion of dilation is sensitive to idomethacin compared to in wild-type mice
  • mice are more sensitive to inhibition of endothelium-derived hyperpolarizing factor associated dilation than wild-type mice
  • mice lack dilation sensitivity to peroxide unlike wild-type mice
  • however, normal flow mediated dilation can be restored with treatment with scavengers for ONOO-
• homeostasis/metabolism phenotype
• abnormal nitric oxide homeostasis (MGI Ref ID J:104082)
  • nitric oxide production in the coronary artery is increased compared to in wild-type mice

Pecam1^{Gt(VICTR20)12Lex}/Pecam1^{Gt(VICTR20)12Lex}

        B6.129S-Pecam1^{Gt(VICTR20)12Lex}/J

• cardiovascular system phenotype
• abnormal vasodilation (MGI Ref ID J:114343)
  • unlike in wild-type mice, vessel dilation is not reduced by L-NAME
  • however, treatment with A23187 (an agonist that stimulates Nos3) restores sensitivity to L-NAME
• decreased vasodilation (MGI Ref ID J:114343)
  • flow mediated dilation of arterioles is reduced compared to in wild-type mice

View Research Applications

Research Applications

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

Cancer Research
Defects in Cell Adhesion Molecules

Cardiovascular Research
Vascular Defects

Cell Biology Research
Defects in Cell Adhesion Molecules

Developmental Biology Research
Defects in Cell Adhesion Molecules

Research Tools
Cardiovascular Research
Internal/Organ Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Pecam1Gt(VICTR20)12Lex
Allele Name		gene trap 12, Lexicon Genetics
Allele Type		Gene trapped
Common Name(s)		Pcamtm1Lex; Pecam1Gt(IRESBetageo)636Lex; Pecamtm1Lex;
Mutation Made By		Ramiro Ramirez-Solls,   Lexicon Genetics Incorporated
Strain of Origin		129S5/SvEvBrd
ES Cell Line Name		Lex-1
ES Cell Line Strain		129S5/SvEvBrd
Gene Symbol and Name		Pecam1, platelet/endothelial cell adhesion molecule 1
Chromosome		11
Gene Common Name(s)		C85791; CD31; CD31 antigen; Cd31; MGC124998; PECAM-1; Pecam; expressed sequence C85791;

Genotyping

Genotyping Information

Genotyping Protocols

Pecam1^{Gt(VICTR20)12Lex}, HRM, vers. 2
Pecam1^{Gt(VICTR20)12Lex}, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Zambrowicz BP; Friedrich GA; Buxton EC; Lilleberg SL; Person C; Sands AT. 1998. Disruption and sequence identification of 2,000 genes in mouse embryonic stem cells. Nature 392(6676):608-11. [PubMed: 9560157]  [MGI Ref ID J:46940]

Additional References

Pecam1^{Gt(VICTR20)12Lex} related

Bagi Z; Frangos JA; Yeh JC; White CR; Kaley G; Koller A. 2005. PECAM-1 mediates NO-dependent dilation of arterioles to high temporal gradients of shear stress. Arterioscler Thromb Vasc Biol 25(8):1590-5. [PubMed: 15890968]  [MGI Ref ID J:114343]

Dusserre N; L'Heureux N; Bell KS; Stevens HY; Yeh J; Otte LA; Loufrani L; Frangos JA. 2004. PECAM-1 interacts with nitric oxide synthase in human endothelial cells: implication for flow-induced nitric oxide synthase activation. Arterioscler Thromb Vasc Biol 24(10):1796-802. [PubMed: 15284089]  [MGI Ref ID J:124576]

Liu Y; Bubolz AH; Shi Y; Newman PJ; Newman DK; Gutterman DD. 2006. Peroxynitrite reduces the endothelium-derived hyperpolarizing factor component of coronary flow-mediated dilation in PECAM-1-knockout mice. Am J Physiol Regul Integr Comp Physiol 290(1):R57-65. [PubMed: 16166207]  [MGI Ref ID J:104082]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. 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

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Contact Information
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

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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.