In contrast to previous investigations regarding the role of Wnt signaling in the experimental hTNFtg mouse model, such as the inhibition of the antagonist DKK1, the loss-of the antagonist WIF1, or treatment with the agonist R-Spondin 1, where soft-tissue inflammatory aspects remained unaffected11,32,34, all aspects of the RA-like symptoms were affected by the loss of Wnt9a. Furthermore, disease progression and severity were augmented in the hTNFtg/+;Wnt9a∆Prx/− mice. The gene discussed is RSPO1; the disease is rheumatoid arthritis.