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; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Edward Goetzl,   Univ of California Medical Center (UCSF)

Description
These "VPAC2 R TG mice" (or VPAC₂R Tg mice) are viable and fertile, harboring the LCK-huVPAC2 transgene. This transgene has the murine lymphocyte protein tyrosine kinase (Lck) proximal promoter directing persistently high expression of huVPAC₂R (human vasoactive intestinal peptide G-protein-coupled receptor 2 [VIPR2 or VIPR₂]) primarily to CD4⁺ T cells (T-helper/inducer cells). As such, expression of huVPAC₂R mRNA and protein is highest in spleen and thymus, but also observed in other tissues at much lower levels. The constitutive high huVPAC₂R expression on CD4⁺ T cells is characteristic of levels usually observed only after maximal TCR stimulation. Transgenic mice have elevated blood IgE, IgG1, and eosinophil levels. The effector T cell phenotype is altered; with Th2-bias cytokine profiles (increased IL-4, IL-5, c-maf and junB) associated with altered hypersensitivity states (increased immediate-type hypersensitivity/decreased delayed-type hypersensitivity). Expression of huVPAC₂R does not significantly alter the number or composition of splenic T cells. Although transgenic mice have more IL-4-secreting CD4⁺ T cells from splenic preparations compared with wildtype mice, the amount of IL-4 secreted per cell is not altered. These VPAC2 R TG mice may be useful as a Th2-bias mouse model for studying innate and adaptive immunity, T cell and macrophage function, allergy and inflammation, and cytokine secretion, as well as immunopathologies related to Th1/Th2 cell ratio imbalance and neuroendocrine/neuroactive peptides in immune function.

Development
The 4.6 kb LCK-huVPAC2 transgene was designed with a murine lymphocyte protein tyrosine kinase (Lck) proximal promoter and full-length human VPAC₂R cDNA (huVPAC2 R or VIPR2; vasoactive intestinal peptide G-protein-coupled receptor 2). This transgene was microinjected into C57BL/6 oocytes, and a male founder animal (founder line unspecified) was bred to C57BL/6 females to establish the transgenic colony. This colony was then maintained by breeding high CD4⁺ T cell VPAC₂R expressing transgenic mice together for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) to establish the colony.

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Lck

002817	B6.129S2-Lcktm1Mak/J
016101	B6.Cg-Il7rtm1Imx Tg(Lck-Il7r)1676Trma/J
013738	B6.Cg-Tg(LCKprBCL2L1)12Sjk/J
012837	B6.Cg-Tg(Lck-cre)3779Nik/J
003802	B6.Cg-Tg(Lck-cre)548Jxm/J
006889	B6.Cg-Tg(Lck-cre)I540Jxm/J
003202	B6;SJL-Tg(CD8aCD8b)57Scr/J
002427	C3H/He-Tg(LCKprBCL2)36Sjk/J
003332	C57BL/6-Tg(LckNotch1)9Erob/J
002230	C57BL/6J-Tg(LckIl4)1315Dbl/J
005732	NOD.Cg-Tg(Lck-cre)548Jxm/AchJ

View Strains carrying other alleles of Lck     (11 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tg(Lck-VIPR2)1Ejg/0

        C57BL/6-Tg(Lck-VIPR2)1Ejg

• immune system phenotype
• decreased interferon-gamma secretion
  • after TCR stimulation splenic CD4+ T cells produce less interferon-gamma (Ifng) than wild-type cells at 24 and 96 hours after stimulation   (MGI Ref ID J:127974)
• decreased susceptibility to type IV hypersensitivity reaction
  • antigen-specific delayed-type hypersensitivity is depressed compared to controls indicated by reduced footpad swelling at 24 hours after immunization with NP OSu   (MGI Ref ID J:127974)
• increased IgE level
  • serum levels are significantly higher than in wild-type   (MGI Ref ID J:127974)
  • levels of antigen-specific IgE during primary and secondary responses to immunization with TNP-KLH are significantly higher than in controls   (MGI Ref ID J:127974)
• increased IgG1 level
  • serum levels are significantly higher than in wild-type   (MGI Ref ID J:127974)
  • levels of antigen-specific IgE during primary and secondary responses to immunization with TNP-KLH are marginally higher than in controls   (MGI Ref ID J:127974)
• increased eosinophil cell number
  • serum levels of eosinophils are significantly higher than in wild-type   (MGI Ref ID J:127974)
• increased interleukin-4 secretion
  • after TCR stimulation splenic CD4+ T cells produce significantly more IL4 than wild-type cells at 24 and 96 hours after stimulation   (MGI Ref ID J:127974)
• increased interleukin-5 secretion
  • after TCR stimulation splenic CD4+ T cells produce significantly more IL5 than wild-type cells at 24 and 96 hours after stimulation   (MGI Ref ID J:127974)
• increased susceptibility to type I hypersensitivity reaction
  • mice show greater immediated cutaneous hypersensitivity to antigen challenge indicated by significantly greater footpad swelling after 60 minutes than in controls   (MGI Ref ID J:127974)
  • much higher active cutaneous anaphylaxis reaction (swelling) is elicited in flank skin of secondarily immunized mice compared to controls at 30 minutes after TNP-CGG challenge   (MGI Ref ID J:127974)
• hematopoietic system phenotype
• increased eosinophil cell number
  • serum levels of eosinophils are significantly higher than in wild-type   (MGI Ref ID J:127974)

View Research Applications

Research Applications

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

Cancer Research
Growth Factors/Receptors/Cytokines

Cell Biology Research
Genes Regulating Growth and Proliferation
Signal Transduction

Developmental Biology Research
Internal/Organ Defects
      Lymphoid Tissue Defects
Lymphoid Tissue Defects

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
Inflammation
Intracellular Signaling Molecules
Lymphoid Tissue Defects
T Cell Receptor Signaling Defects

Internal/Organ Research
Lymphoid Tissue Defects

Research Tools
Cancer Research
      T cell deficiency
      specific T cell deficiency
Immunology and Inflammation Research
      Macrophage Deficiency
      T cell deficiency
      genes regulating susceptibility to infectious disease and endotoxin
      production of T cell lines and hybridomas
      specific T cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(Lck-VIPR2)1Ejg
Allele Name		transgene insertion 1, Edward J Goetzl
Allele Type		Transgenic (random, expressed)
Common Name(s)		LCK-huVPAC2; LCK-huVPAC2R; huVPAC2 R;
Mutation Made By		Edward Goetzl,   Univ of California Medical Center (UCSF)
Strain of Origin		C57BL/6
Expressed Gene		VIPR2, vasoactive intestinal peptide receptor 2, human
Promoter		Lck, lymphocyte protein tyrosine kinase, mouse, laboratory
Molecular Note		A murine lymphocyte protein tyrosine kinase (Lck) proximal promoter was used to drive the full-length human VPAC2R cDNA (huVPAC2 R or VIPR2; vasoactive intestinal peptide G-protein-coupled receptor 2). This transgene was microinjected into C57BL/6 oocytes, and a male founder animal was bred to C57BL/6 females to establish the line. [MGI Ref ID J:127974]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Lck-VIPR2), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Voice J; Donnelly S; Dorsam G; Dolganov G; Paul S; Goetzl EJ. 2004. c-Maf and JunB mediation of Th2 differentiation induced by the type 2 G protein-coupled receptor (VPAC2) for vasoactive intestinal peptide. J Immunol 172(12):7289-96. [PubMed: 15187104]  [MGI Ref ID J:90832]

Voice JK; Dorsam G; Lee H; Kong Y; Goetzl EJ. 2001. Allergic diathesis in transgenic mice with constitutive T cell expression of inducible vasoactive intestinal peptide receptor. FASEB J 15(13):2489-96. [PubMed: 11689474]  [MGI Ref ID J:127974]

Additional References

Tg(Lck-VIPR2)1Ejg related

Voice JK; Grinninger C; Kong Y; Bangale Y; Paul S; Goetzl EJ. 2003. Roles of vasoactive intestinal peptide (VIP) in the expression of different immune phenotypes by wild-type mice and T cell-targeted type II VIP receptor transgenic mice. J Immunol 170(1):308-14. [PubMed: 12496414]  [MGI Ref ID J:127285]

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, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, hemizygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice. The donating investigator reports breeding homozygous mice together.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Noncarrier
	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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