Description

Strain Information

Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   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
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
004782	STOCK Tg(KRT14-cre)1Amc/J
005107	STOCK Tg(KRT14-cre/Esr1)20Efu/J

View Strains carrying other alleles of KRT14     (10 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tg(KRT14-Vegfa)3Dtm/0

        FVB/N-Tg(KRT14-Vegfa)3Dtm

• homeostasis/metabolism phenotype
• delayed wound healing (MGI Ref ID J:111924)
  • despite increased angiogenesis and vasculogenesis, wound closure is slightly delayed in transgenic mice compared to wild-type
• skin edema (MGI Ref ID J:92643)
  • pronounced in dermis after oxazolone challenge
• immune system phenotype
• abnormal leukocyte adhesion (MGI Ref ID J:104245)
  • mice display enhanced density of adherent leukocytes (251.9/mm² vs 61.3/mm² in wild-type)
• abnormal leukocyte rolling (MGI Ref ID J:104245)
  • postcapillary venules show an increased proportion of rolling leukocytes compared to venules in wild-type skin (47.9% vs 15.6%, respectively)
• abnormal lymph node cellularity (MGI Ref ID J:92643)
  • 24 hours after oxazolone challenge, lymph nodes draining the challenges side of transgenics are enlarged
• abnormal lymphatic vessel morphology (MGI Ref ID J:92643)
  • mutants show enlarged dermal lymphatics in non-inflamed skin compared to wild-type
  • lymphatic vessels are significantly larger in mutants (935 um² compared to wild-type, 592 um²) 30 days after DTH induction
  • 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
  • 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
• enlarged lymph nodes (MGI Ref ID J:92643)
  • 24 hours after oxazolone challenge, lymph nodes draining the challenges side of transgenics are enlarged
• increased macrophage cell number (MGI Ref ID J:111924)
  • 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
• increased mast cell number (MGI Ref ID J:104245)
  • there is increased mast cell localization to sites of angiogenesis compared to controls (35% increase in mast cell density compared to wild-type)
• hematopoietic system phenotype
• increased macrophage cell number (MGI Ref ID J:111924)
  • 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
• increased mast cell number (MGI Ref ID J:104245)
  • there is increased mast cell localization to sites of angiogenesis compared to controls (35% increase in mast cell density compared to wild-type)
• cardiovascular system phenotype
• abnormal angiogenesis (MGI Ref ID J:104245)
  • 3-week old transgenic mice show increased angiogenesis in the skin
  • mutants have significantly higher numbers of blood vessels in normal skin compared to wild-type
  • 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
  • vascularization of granulation tissue remains elevated for three weeks following wounding, compared to control mice
• abnormal capillary morphology (MGI Ref ID J:104245)
  • 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
• increased vascular permeability (MGI Ref ID J:104245)
  • induced new dermal capillaries in the ear skin are hyperpermeable
  • extravasation of dye in non-inflamed ears of transgenic mice is significantly higher (34 ng/mg) than wild-type (7 ng/mg)
  • 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
• skin/coat/nails phenotype
• abnormal epidermal layer morphology (MGI Ref ID J:92643)
  • epidermis contains fingerlike, anatomosing extensions protruding into the dermis after oxazolone challenge
• epidermal hyperplasia (MGI Ref ID J:92643)
  • 1 month after oxazolone challenge, ears display epidermal hyperplasia
• parakeratosis (MGI Ref ID J:92643)
  • epidermis of the ears is parakeratotic 1 month after oxazolone challenge
• mixed cellular infiltration to dermis (MGI Ref ID J:92643)
  • dense inflammatory infiltrates of CD4+ lymphocytes within the dermis, as well as CD8+ lymphocytes within the epidermis
• psoriasis (MGI Ref ID J:92643)
  • 1 month after oxazolone challenge, ears of mice show a psoriasis-like phenotype
• skin edema (MGI Ref ID J:92643)
  • pronounced in dermis after oxazolone challenge

View Research Applications

Research Applications

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

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

Dermatology Research
Skin and Hair Texture Defects (psoriasis)

Immunology and Inflammation Research
Inflammation (rheumatoid arthritis)
Lymphoid Tissue Defects

Internal/Organ Research
Wound Healing

Research Tools
Dermatology Research

Genes & Alleles

Gene & Allele Information

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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

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

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
	Noncarrier
	001800 FVB/NJ
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

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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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Terms of Use

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fax:	207-288-6655

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