Genetic control of experimental spondylarthropathy




To characterize experimentally induced spondylarthropathy (SpA) in arthritis-susceptible inbred mice and in their F1 and F2 hybrid generations of susceptible and resistant mouse strains.


SpA was induced in susceptible BALB/c and C3H/HeJCr (C3H) strains of mice, and in their F1 and F2 generations derived from intercrosses with arthritis- and/or spondylitis-resistant DBA/2 and DBA/1 parent strains, by systemic immunization with cartilage proteoglycan (PG) aggrecan. The incidence and severity of PG-induced spondylitis (PGIS) were scored histologically, and these scores for spine involvement were correlated with serum antibody and cytokine levels and with in vitro T cell responses to cartilage PG.


PGIS was induced by systemic immunization with cartilage PG in adjuvant, and ∼60–70% of susceptible mouse strains and their F2 hybrids developed spondylitis either with or without arthritis. Adjuvants, particularly those activating the innate immune system and enforcing the Th1 dominance, had significant effects on the outcome and progression of SpA. The DBA/1 strain appeared to carry genes protecting this strain and its F1 and F2 hybrids from spondylitis, whereas the DBA/2 strain, although resistant to PGIS, harbored genes permitting PGIS in its hybrid generations. Arthritis- and/or spondylitis-susceptible BALB/c and C3H parent strains and their F2 hybrids exhibited the highest incidence and severity of spondylitis.


PGIS, a murine model of autoimmune spondylitis, shows similarities to ankylosing spondylitis. Segregation of susceptibility to PG-induced arthritis (PGIA) from that to PGIS in different genetic crosses suggests that PGIA and PGIS are separate diseases. Therefore, this model allows for the elucidation of genetic components involved in the etiology of SpA, independent of those controlling the susceptibility to PGIA.