Development of spontaneous arthritis in beta2-microglobulin-deficient mice without expression of HLA-B27: association with deficiency of endogenous major histocompatibility complex class I expression [In Process Citation]
Arthritis Rheum 2000 Oct; 43(10):2290-6.
OBJECTIVE: Mice deficient in beta2-microglobulin (beta2m), but expressing the human major histocompatibility complex (MHC) class I molecule HLA-B27, have been reported to develop spontaneous inflammatory arthritis (SA). We sought to determine whether, under certain conditions, beta2m deficiency alone was sufficient to cause SA, and if this might be a result of class I deficiency. METHODS: The following types of mice were produced: mice of the MHC b haplotype genetically deficient in beta2m (beta2m(0)) on several genetic backgrounds (C57BL/6J [B6], BALB/cJ, SJL/J, MRL/MpJ, and B6,129), mice deficient in the transporter associated with antigen processing (TAP1(0)) on a B6,129 background, and HLA-B27-transgenic beta2m(0) mice on a B6 background. Cohorts were transferred from specific pathogen-free (SPF) to conventional (non-SPF) animal rooms, and evaluated clinically and histologically for the development of SA. RESULTS: SA occurred in TAP1(0) and beta2m(0)/class I-deficient mice with a mixed B6,129 genome at a developed this arthropathy. MRL/ MpJ beta2m(0) mice were unaffected. Expression of B27 did not increase the frequency of SA in B27-transgenic B2m(0) B6 mice compared with that in beta2m(0) B6 controls. CONCLUSION: Class I deficiency is sufficient to cause SA in mice. The frequency of disease, as well as B27-specific SA, is markedly dependent on a non-MHC genetic background. These results suggest that class I deficiency in a genetically susceptible mouse can mimic B27-associated arthropathy.
Kingsbury, D J.; Mear, J P.; Witte, D P.; Taurog, J D.; Roopenian, D C.; and Colbert, R A., " Development of spontaneous arthritis in beta2-microglobulin-deficient mice without expression of HLA-B27: association with deficiency of endogenous major histocompatibility complex class I expression [In Process Citation]" (2000). Faculty Research 2000 - 2009. 124.