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 Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System +/+ sibling x Hemizygote         (Female x Male)   01-JUN-10 Species laboratory mouse Generation N13p (19-FEB-06) Generation Definitions   Donating Investigator Michael Detmar,   Swiss Fed Institute of Tech (ETH) Zurich

Description
Mice hemizygous for the transgene are viable and fertile. Transgene expression is demonstrated in the basal keratinocyte layer of the epidermis and outer root sheath keratinocytes of hair follicles. Homozygous mice spontaneously develop severe psoriasis-like lesions between 3-6 months of age, where hemizygous mice do not. Transgenic mice have increased density of tortuous cutaneous blood capillaries with elevated expression of select VEGF receptors, most prominently in neonates. Dermal mast cell localization and capillary hyperpermeability are also increased. Postcapillary venules exhibit significantly enhanced leukocyte rolling and adhesion. Transgenic expression promotes lymphangiogenesis associated not only with delayed-type hypersensitivity induced psoriasis-like skin inflammation but also with cutaneous tissue repair after wounding. Further, transgenic mice have accelerated chemically induced skin carcinogenesis with tumor associated lymphangiogenesis and angiogenesis. Elevated metastasis to sentinel and distal lymph nodes and organs is observed. Depilated transgenic mice have accelerated hair regrowth compared to wildtype. Mice expressing this transgene may be useful in studying psoriasis, contact dermatitis, rheumatoid arthritis, lymphangiogenesis, cancer, or hair growth.

Development
A murine cDNA coding for the 164-amino acid Vegfa splice variant was ligated into the human keratin 14 expression cassette. The resulting construct, keratin 14 promoter-controlled Vegfa₁₆₄, was injected into FVB/N zygotes and transplanted into pseudopregnant C21 foster mothers. Chimeric males (founder line 3) were bred to FVB/N females. Hemizygous pups were intercrossed to establish homozygotes. Homozygous mice were intercrossed for more than 12 generations before arrival at The Jackson Laboratory.

Control Information

	Control
	Noncarrier
	001800 FVB/NJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of KRT14

006403	129S.B6-Tg(KRT14-Esr1/HRAS)1Pkha/J
006661	129S.B6-Tg(KRT14-RAF1/ESR1)1Pkha/J
004853	B6.C3-Tg(KRT14-Birc5)19Gros/J
009687	B6.Cg-Tg(KRT14-Kitl*)4XTG2Bjl/J
007622	B6;SJL-Tg(KRT14-Hr)551Cct/J
007678	B6;SJL-Tg(KRT14-rtTA)208Jek/J
002980	C57BL/6-Tg(Cd152Ig)1Jbs/J
006822	FVB-Tg(KRT14-MAP2K1/Esr1)12Pkha/J
008099	FVB-Tg(KRT14-rtTA)F42Efu/J
017005	FVB.Cg-Tg(KRT14-Fyn*)aJsey/J
004782	STOCK Tg(KRT14-cre)1Amc/J
005107	STOCK Tg(KRT14-cre/ERT)20Efu/J

View Strains carrying other alleles of KRT14     (12 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Microvascular Complications of Diabetes, Susceptibility to, 1; MVCD1   (VEGFA) Vascular Endothelial Growth Factor A; VEGFA   (VEGFA)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tg(KRT14-Vegfa)3Dtm/0

        FVB/N-Tg(KRT14-Vegfa)3Dtm

• homeostasis/metabolism phenotype
• delayed wound healing
  • despite increased angiogenesis and vasculogenesis, wound closure is slightly delayed in transgenic mice compared to wild-type   (MGI Ref ID J:111924)
• skin edema
  • pronounced in dermis after oxazolone challenge   (MGI Ref ID J:92643)
• immune system phenotype
• abnormal leukocyte adhesion
  • mice display enhanced density of adherent leukocytes (251.9/mm² vs 61.3/mm² in wild-type)   (MGI Ref ID J:104245)
• abnormal leukocyte tethering or rolling
  • postcapillary venules show an increased proportion of rolling leukocytes compared to venules in wild-type skin (47.9% vs 15.6%, respectively)   (MGI Ref ID J:104245)
• abnormal lymphatic vessel morphology
  • transgenic mice rapidly form a lymphatic vasculature at the site of the wound whereas no lymphatic vessels are found at day 7 post-wounding and only a few sprouting vessels are seen at day 10 in wild-type mice   (MGI Ref ID J:111924)
• • enlarged lymphatic vessel
    • mutants show enlarged dermal lymphatics in non-inflamed skin compared to wild-type   (MGI Ref ID J:92643)
    • lymphatic vessels are significantly larger in mutants (935 um² compared to wild-type, 592 um²) 30 days after DTH induction   (MGI Ref ID J:92643)
    • after induction of delayed-type hypersensitivity (DTH) reactions, skin of wild-type mice show tissue edema and a transient enlargement of lymphatic vessels which declines after 7 days and returns to baseline in 1 month; mutants show prolonged ear-swelling, and enhanced and persistent lymphatic vessel enlargement still detectable 1 month after initiation   (MGI Ref ID J:92643)
• enlarged lymph nodes
  • 24 hours after oxazolone challenge, lymph nodes draining the challenges side of transgenics are enlarged   (MGI Ref ID J:92643)
• increased macrophage cell number
  • number of macrophages in granulation tissue is increased 2-fold compared to wild-type at day 7 after wounding but at days 10 and 14, numbers are equivalent to wild-type   (MGI Ref ID J:111924)
• increased mast cell number
  • there is increased mast cell localization to sites of angiogenesis compared to controls (35% increase in mast cell density compared to wild-type)   (MGI Ref ID J:104245)
• hematopoietic system phenotype
• increased macrophage cell number
  • number of macrophages in granulation tissue is increased 2-fold compared to wild-type at day 7 after wounding but at days 10 and 14, numbers are equivalent to wild-type   (MGI Ref ID J:111924)
• increased mast cell number
  • there is increased mast cell localization to sites of angiogenesis compared to controls (35% increase in mast cell density compared to wild-type)   (MGI Ref ID J:104245)
• cardiovascular system phenotype
• abnormal angiogenesis
  • 3-week old transgenic mice show increased angiogenesis in the skin   (MGI Ref ID J:104245)
  • mutants have significantly higher numbers of blood vessels in normal skin compared to wild-type   (MGI Ref ID J:92643)
  • transgenic mice display an increased density of blood microvessels in the dermis of the abdomen, dorsal region and ear at 3 days of age compared to controls; increase is less dramatic at 11 days, 3 weeks and 6 weeks   (MGI Ref ID J:104245)
  • vascularization of granulation tissue remains elevated for three weeks following wounding, compared to control mice   (MGI Ref ID J:111924)
• abnormal capillary morphology
  • in 3-week old transgenics, capillaries in the skin show a highly increased tortuosity index (+69%) compared to wild-type with a corresponding average decreased length without branching   (MGI Ref ID J:104245)
• increased vascular permeability
  • induced new dermal capillaries in the ear skin are hyperpermeable   (MGI Ref ID J:104245)
  • extravasation of dye in non-inflamed ears of transgenic mice is significantly higher (34 ng/mg) than wild-type (7 ng/mg)   (MGI Ref ID J:92643)
  • 24 hours after oxazolone challenge, baseline leakage increased 10 fold in wild-type and 11.5-fold in transgenic animals compared to vehicle-treated mice; 7 days after treatment leakage is diminished in wild-type and mutant mice but is still much higher in mutants   (MGI Ref ID J:92643)
• integument phenotype
• abnormal epidermal layer morphology
  • epidermis contains fingerlike, anatomosing extensions protruding into the dermis after oxazolone challenge   (MGI Ref ID J:92643)
• • epidermal hyperplasia
    • 1 month after oxazolone challenge, ears display epidermal hyperplasia   (MGI Ref ID J:92643)
  • parakeratosis
    • epidermis of the ears is parakeratotic 1 month after oxazolone challenge   (MGI Ref ID J:92643)
• mixed cellular infiltration to dermis
  • dense inflammatory infiltrates of CD4+ lymphocytes within the dermis, as well as CD8+ lymphocytes within the epidermis   (MGI Ref ID J:92643)
• psoriasis
  • 1 month after oxazolone challenge, ears of mice show a psoriasis-like phenotype   (MGI Ref ID J:92643)
• skin edema
  • pronounced in dermis after oxazolone challenge   (MGI Ref ID J:92643)
• cellular phenotype
• abnormal leukocyte adhesion
  • mice display enhanced density of adherent leukocytes (251.9/mm² vs 61.3/mm² in wild-type)   (MGI Ref ID J:104245)
• abnormal leukocyte tethering or rolling
  • postcapillary venules show an increased proportion of rolling leukocytes compared to venules in wild-type skin (47.9% vs 15.6%, respectively)   (MGI Ref ID J:104245)

View Research Applications

Research Applications

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

Cancer Research
Increased Tumor Incidence
      Skin Cancers
      Skin Cancers: Induced
Other
      tumor metastasis

Dermatology Research
Skin and Hair Texture Defects
      psoriasis

Immunology, Inflammation and Autoimmunity Research
Inflammation
      rheumatoid arthritis
Lymphoid Tissue Defects

Internal/Organ Research
Wound Healing

Research Tools
Dermatology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(KRT14-Vegfa)3Dtm
Allele Name		transgene insertion 3, Michael Detmar
Allele Type		Transgenic (random, expressed)
Common Name(s)		K14-VEGF; K14/VEGF-A;
Mutation Made By		Michael Detmar,   Swiss Fed Institute of Tech (ETH) Zurich
Strain of Origin		FVB/N
Expressed Gene		Vegfa, vascular endothelial growth factor A, mouse, laboratory
Promoter		KRT14, keratin 14, human
General Note		Phenotypic Similarity to Human Syndrome: Psoriasis
Molecular Note		cDNA encoding murine VEGF164 was inserted behind a keratin-14 expression cassette. The purified construct was injected into fertilized FVB/N embryos that were implanted into pseudo-pregnant C21 females. In situ analysis of transgenic mice confired selectively increased VEGF expression in the basal keratinocyte layer of the epidermis and in outer sheath keratinocytes of hair follicles. [MGI Ref ID J:104245]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(KRT14-Vegfa)3Dtm, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Detmar M; Brown LF; Schon MP; Elicker BM; Velasco P; Richard L; Fukumura D; Monsky W; Claffey KP; Jain RK. 1998. Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. J Invest Dermatol 111(1):1-6. [PubMed: 9665379]  [MGI Ref ID J:104245]

Additional References

Tg(KRT14-Vegfa)3Dtm related

Halin C; Fahrngruber H; Meingassner JG; Bold G; Littlewood-Evans A; Stuetz A; Detmar M. 2008. Inhibition of chronic and acute skin inflammation by treatment with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Am J Pathol 173(1):265-77. [PubMed: 18535184]  [MGI Ref ID J:137380]

Hong YK; Lange-Asschenfeldt B; Velasco P; Hirakawa S; Kunstfeld R; Brown LF; Bohlen P; Senger DR; Detmar M. 2004. VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the alpha1beta1 and alpha2beta1 integrins. FASEB J 18(10):1111-3. [PubMed: 15132990]  [MGI Ref ID J:111924]

Hvid H; Teige I; Kvist PH; Svensson L; Kemp K. 2008. TPA induction leads to a Th17-like response in transgenic K14/VEGF mice: a novel in vivo screening model of psoriasis. Int Immunol 20(8):1097-106. [PubMed: 18579711]  [MGI Ref ID J:138891]

Kajiya K; Hirakawa S; Detmar M. 2006. Vascular endothelial growth factor-A mediates ultraviolet B-induced impairment of lymphatic vessel function. Am J Pathol 169(4):1496-503. [PubMed: 17003502]  [MGI Ref ID J:113381]

Kunstfeld R; Hirakawa S; Hong YK; Schacht V; Lange-Asschenfeldt B; Velasco P; Lin C; Fiebiger E; Wei X; Wu Y; Hicklin D; Bohlen P; Detmar M. 2004. Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia. Blood 104(4):1048-57. [PubMed: 15100155]  [MGI Ref ID J:92643]

Roudnicky F; Poyet C; Wild P; Krampitz S; Negrini F; Huggenberger R; Rogler A; Stohr R; Hartmann A; Provenzano M; Otto VI; Detmar M. 2013. Endocan is upregulated on tumor vessels in invasive bladder cancer where it mediates VEGF-A-induced angiogenesis. Cancer Res 73(3):1097-106. [PubMed: 23243026]  [MGI Ref ID J:194365]

Teige I; Hvid H; Svensson L; Kvist PH; Kemp K. 2009. Regulatory T cells control VEGF-dependent skin inflammation. J Invest Dermatol 129(6):1437-45. [PubMed: 19037231]  [MGI Ref ID J:151057]

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 maintained as homozygotes.
Mating System	+/+ sibling x Hemizygote         (Female x Male)   01-JUN-10

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
	Noncarrier
	001800 FVB/NJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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