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.
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.


CONCLUSIONS
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
DJ
Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Mear
J P
JP
Witte
D P
DP
Taurog
J D
JD
Roopenian
D C
DC
Colbert
R A
RA
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology; D001168:Arthritis / Q000209:etiology* / Q000276:immunology; D005260:Female; D015796:HLA-B27 Antigen / Q000096:biosynthesis*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D001613:beta 2-Microglobulin / Q000172:deficiency*
D000954:Antigens, Surface; D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin