Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin: a model of human spondyloarthropathies.
Human class I major histocompatibility complex allele HLA-B27 is associated with a group of human diseases called "spondyloarthropathies." Studies on transgenic rats expressing HLA-B27 and human beta 2-microglobulin have confirmed the role of HLA-B27 in disease pathogenesis. Here we report spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin (B27+ beta 2m-/-). In the absence of beta 2-microglobulin, B27+ beta 2m-/- animals do not express the HLA-B27 transgene on the cell surface and have a very low level of CD8+ T cells. Most of the B27+ beta 2m-/- male mice showed nail changes, hair loss, and swelling in paws, which leads to ankylosis. The symptoms occur only after the B27+ beta 2m-/- mice are transferred from the specific pathogen-free mouse colony. These results suggest that aberrant assembly, transport, and expression of the HLA-B27 molecule may predispose an individual for development of the disease when exposed to an appropriate environmental trigger.
Khare
S D
SD
Department of Immunology, Mayo Clinic and Medical School, Rochester, Minnesota 55902, USA.
Luthra
H S
HS
David
C S
CS
D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D005121:Extremities / Q000473:pathology; D015796:HLA-B27 Antigen / Q000235:genetics*; D006197:Hair / Q000473:pathology; D007249:Inflammation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009262:Nails / Q000473:pathology; D011499:Protein Processing, Post-Translational; D013167:Spondylitis, Ankylosing / Q000209:etiology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics*
D015796:HLA-B27 Antigen; D001613:beta 2-Microglobulin