Development of spontaneous arthritis in β2-microglobulin–deficient mice without expression of HLA–B27: Association with deficiency of endogenous major histocompatibility complex class I expression
✍ Scribed by Daniel J. Kingsbury; John P. Mear; David P. Witte; Joel D. Taurog; Derry C. Roopenian; Robert A. Colbert
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 368 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
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 frequency of 30-50%, while 10-15% of b6, sjl/j, and balb/cj beta2m(0) mice 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.