C57BL/6-Tg(Lck-VIPR2)1Ejg/J

Stock number: 008842
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These "VPAC2 R TG mice" (or VPAC₂ Tg mice) have 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 primarily to CD4⁺ T cells at levels typically observed only after maximal TCR stimulation, and 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.

Detailed 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.

Allele

Symbol: Tg(Lck-VIPR2)1Ejg
Name: transgene insertion 1, Edward J Goetzl
MGI accession ID: MGI:3819792
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Lck-VIPR2)1Ejg
Marker name: transgene insertion 1, Edward J Goetzl
Chromosome: UN
Strain of origin: C57BL/6
Expressed genes: VIPR2,vasoactive intestinal peptide receptor 2,human
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.