However, this hypothesis is now recognized as oversimplistic and has been challenged by various studies utilizing dimerization deficient GRdim mice with a single point mutation that impairs GR dimerization.211 These studies have found GRdim mice are highly susceptible to sepsis characterized by increased pro-inflammatory cytokine expression and are resistant to GC treatment in an antigen-induced arthritis model of RA.212–215 Thus, these studies demonstrate that GR dimerization has essential anti-inflammatory effects in both septic shock and arthritis. This evidence concerns the gene NR3C1 and arthritic joint disease.