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.
