TY - JOUR
T1 - Development of spontaneous arthritis in β2-microglobulin-deficient mice without expression of HLA-B27
T2 - Association with deficiency of endogenous major histocompatibility complex class I expression
AU - Kingsbury, Daniel J.
AU - Mear, John P.
AU - Witte, David P.
AU - Taurog, Joel D.
AU - Roopenian, Derry C.
AU - Colbert, Robert A.
PY - 2000
Y1 - 2000
N2 - Objective. Mice deficient in β2-microglobulin (β2m), 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, β2m 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 β2m (β2m0) 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 (TAP10) on a B6,129 background, and HLA-B27-transgenic β2m0 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 TAP10 and β2m0/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 β2m0 mice developed this arthropathy. MRL/MpJ β2m0 mice were unaffected. Expression of B27 did not increase the frequency of SA in B27-transgenic β2m0 B6 mice compared with that in β2m0 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.
AB - Objective. Mice deficient in β2-microglobulin (β2m), 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, β2m 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 β2m (β2m0) 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 (TAP10) on a B6,129 background, and HLA-B27-transgenic β2m0 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 TAP10 and β2m0/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 β2m0 mice developed this arthropathy. MRL/MpJ β2m0 mice were unaffected. Expression of B27 did not increase the frequency of SA in B27-transgenic β2m0 B6 mice compared with that in β2m0 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.
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U2 - 10.1002/1529-0131(200010)43:10<2290::AID-ANR17>3.0.CO;2-6
DO - 10.1002/1529-0131(200010)43:10<2290::AID-ANR17>3.0.CO;2-6
M3 - Article
C2 - 11037889
AN - SCOPUS:0033789614
SN - 0004-3591
VL - 43
SP - 2290
EP - 2296
JO - Arthritis and rheumatism
JF - Arthritis and rheumatism
IS - 10
ER -