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

Former Names B6.129S-Pecam1Gt((OST16303)Lex/J    (Changed: 20-MAR-09 ) B6.129S-Pecam1Gt(VICTR20)12Lex/J    (Changed: 16-JAN-09 ) Type Congenic; Gene Trap; 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 Generation N10F1+N1p Generation Definitions   Donating Investigator John A 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

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Pecam1^{Gt(OST16303)Lex}/Pecam1^{Gt(OST16303)Lex}

        B6.129S5-Pecam1^{Gt(OST16303)Lex}

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

Pecam1^{Gt(OST16303)Lex}/Pecam1^{Gt(OST16303)Lex}

        B6.129S-Pecam1^{Gt(OST16303)Lex}/J

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

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 provided by MGI

Allele Symbol		Pecam1Gt(OST16303)Lex
Allele Name		gene trap OST16303, Lexicon Genetics
Allele Type		Gene trapped
Common Name(s)		Pcamtm1Lex; Pecam1Gt(IRESBetageo)636Lex; Pecam1Gt(VICTR20)12Lex; 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/EndoCAM; Cd31; GPIIA'; PECA1; PECAM-1; Pecam; endoCAM; expressed sequence C85791;

Genotyping

Genotyping Information

Genotyping Protocols

Pecam1^{Gt(VICTR20)12Lex}, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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(OST16303)Lex} 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]

Ieronimakis N; Hays A; Reyes M. 2012. Bone marrow-derived cells do not engraft into skeletal muscle microvasculature but promote angiogenesis after acute injury. Exp Hematol 40(3):238-249.e3. [PubMed: 22155292]  [MGI Ref ID J:191531]

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]

Otte LA; Bell KS; Loufrani L; Yeh JC; Melchior B; Dao DN; Stevens HY; White CR; Frangos JA. 2009. Rapid changes in shear stress induce dissociation of a G alpha(q/11)-platelet endothelial cell adhesion molecule-1 complex. J Physiol 587(Pt 10):2365-73. [PubMed: 19332487]  [MGI Ref ID J:176541]

Stevens HY; Melchior B; Bell KS; Yun S; Yeh JC; Frangos JA. 2008. PECAM-1 is a critical mediator of atherosclerosis. Dis Model Mech 1(2-3):175-81. [PubMed: 19048083]  [MGI Ref ID J:142083]

Zambrowicz BP; Abuin A; Ramirez-Solis R; Richter LJ; Piggott J; BeltrandelRio H; Buxton EC; Edwards J; Finch RA; Friddle CJ; Gupta A; Hansen G; Hu Y; Huang W; Jaing C; Key BW Jr; Kipp P; Kohlhauff B; Ma ZQ; Markesich D; Payne R; Potter DG; Qian N; Shaw J; Schrick J; Shi ZZ; Sparks MJ; Van Sligtenhorst I; Vogel P; Walke W; Xu N; Zhu Q; Person C; Sands AT. 2003. Wnk1 kinase deficiency lowers blood pressure in mice: a gene-trap screen to identify potential targets for therapeutic intervention. Proc Natl Acad Sci U S A 100(24):14109-14. [PubMed: 14610273]  [MGI Ref ID J:86696]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	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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