Inducible expression of transgenic human TNFα in adult mice develops psoriatic-like arthritis.

Retser E, Schied T, Skryabin BV, Vogl T, Kanczler JM, Hamann N, Niehoff A, Hermann S, Eisenblätter M, Wachsmuth L, Pap T, van Lent P, Loser K, Roth J, Zaucke F, Ludwig S, Wixler V

Zusammenfassung

Objective: Generation of inducible TNFα transgenic mice to overcome a major disadvantage of existing transgenic mice with constitutive expression of TNFα: the limitation in crossing them with various knockout or transgenic mice. Methods: A transgenic mouse line that expresses the human TNFα cytokine exclusively after doxycycline administration was generated and analyzed for the onset of diseases. Results: The inducible ihTNFtg mice developed an inflammatory arthritis- and psoriasis-like phenotype with fore and hind paws being prominently affected. The formation of "sausage"-like digits with obligatory involvement of the distal interphalangeal joints and nail malformation was very characteristic. Synovial hyperplasia, enthesitis, cartilage and bone alterations, formation of pannus tissue as well as inflammation of the skin epidermis and nail matrix appeared as early as one week after the treatment of mice with doxycycline and became aggravated over time. The abrogation of hTNFα by the removal of doxycycline six weeks after beginning stimulation resulted in a fast resolution of the most accomplished macroscopic and histological disorders and three to six weeks later only minimal signs of the disease were visible. Conclusions: On doxycycline administration the ihTNFtg mouse displays the major features of inflammatory arthritis. It represents a unique animal model for studying the molecular mechanisms of arthritis, especially the early phases of disease genesis and tissue remodeling steps on abrogation of TNFα expression. Furthermore, unlimited crossing of the ihTNFtg mice with various knockout or transgenic mice opens new possibilities for unraveling the role of various signaling molecules acting in concert with TNFα. © 2013 American College of Rheumatology.