To gain insights regarding the specific roles of the different α2-AR subtypes in these processes, we evaluated, in the present study, the bone phenotype of mice with the global single gene inactivation of α2C-AR subtype (α2C-AR-/- mice), and the skeletal responses of these KO animals to chronic conditions of TH excess (30 or 90 days of thyrotoxicosis). The gene discussed is ADORA2A; the disease is thyrotoxicosis.