The peripheral cannabinoid receptor knockout mice: an update

Abstract

This review gives an overview of the CB2 receptor (CB2R) knockout (CB2R-/-) mice phenotype and the work that has been carried out using this mutant mouse. Using the CB2R-/- mice, investigators have discovered the involvement of CB2R on immune cell function and development, infection, embryonic development, bone loss, liver disorders, pain, autoimmune inflammation, allergic dermatitis, atherosclerosis, apoptosis and chemotaxis. Using the CB2R-/- mice, investigators have also found that this receptor is not involved in cannabinoid-induced hypotension. In addition, the CB2R-/- mice have been used to determine specific tissue CB2R expression. The specificity of synthetic cannabinoid agonists, antagonists and anti-CB2R antibodies has been screened using tissues from CB2R-/- mice. Thus, the use of this mouse model has greatly helped reveal the diverse events involving the CB2R, and has aided in drug and antibody screening.

Figure 1

Cannabinoids inhibited the secretion of interleukin-2 (IL-2) in CB₂R^+/+ and CB₂R^−/− splenocytes stimulated with concanavalin A (Con A). CB₂R^+/+ or CB₂R^−/− splenocytes (1 × 10⁶ cells per ml per well) were stimulated with Con A (2.5 μg ml⁻¹) and treated with the indicated concentrations of 2-arachidonoylglycerol (2-AG) (a) or WIN 55,212-2 (b). IL-2 secretion levels were determined from 72-h cell culture supernatants by ELISA. Data are expressed as the mean of triplicate samples ±s.d. and are representative of three independent experiments. ^*Significantly different from untreated control, P<0.05.

Figure 2

Cannabinoid inhibited the secretion of interferon-γ (IFN-γ) in CB₂R^+/+ and CB₂R^−/− splenocytes stimulated with concanavalin A (Con A). CB₂R^+/+ or CB₂R^−/− splenocytes (1 × 10⁶ cells per ml per well) were stimulated with Con A (2.5 μg ml⁻¹) and treated with the indicated concentrations of 2-arachidonoylglycerol (2-AG) (a) or WIN 55,212-2 (b). IFN-γ secretion levels were determined from 72-h cell culture supernatants by ELISA. Data are expressed as the mean of triplicate samples ±s.d. and are representative of three independent experiments. ^*Significantly different from untreated control, P<0.05.

Figure 3

Using the CB₂R^−/− mice, the CB₂R has been implicated in diverse diseases.