HLA-B27 as a relative risk factor in ankylosing enthesopathy in transgenic mice

The role of MHC class I heterodimer expression in mouse ankylosing enthesopathy

“…It was previously shown that a transgene for HLA-B*2702 is a relative risk factor for ANKENT, reaching the highest significance in H2 b mice (relative risk 9.4, P50.025, (Weinreich et al 1995a). Doubly transgenic mice with hu-β2m in addition to HLA-B*2702 have higher cell-membrane expression of HLA-B2702, but no increased risk for ANKENT as compared with HLA-B*2702 singly trangenic littermates (Weinreich et al 1995a;Chopin et al 1996).…”

“…A helpful tool in questioning the pathogenic effect of the HLA-B27 molecule are transgenic and knockout (ko) animals. Our group has previously described a model for B27-associated joint disease called mouse ankylosing enthesopathy [(ANKENT) (Weinreich et al 1995a)]. ANK-ENT is a naturally occurring joint disease characterized by progressive ankylosis of the entheses in the ankle and tarsal joints of the hind paw.…”

“…ANK-ENT is a naturally occurring joint disease characterized by progressive ankylosis of the entheses in the ankle and tarsal joints of the hind paw. The prevalence, pathology, and genetic risk factors for this disease have been described (Weinreich et al 1995a), as well as the existence of environmental risk factors (Weinreich et al 1995b(Weinreich et al , 1996. The pathology of ANKENT has remarkable similarities to that of human ankylosing spondylitis (Weinreich et al 1995a).…”

“…The prevalence, pathology, and genetic risk factors for this disease have been described (Weinreich et al 1995a), as well as the existence of environmental risk factors (Weinreich et al 1995b(Weinreich et al , 1996. The pathology of ANKENT has remarkable similarities to that of human ankylosing spondylitis (Weinreich et al 1995a). Also, it has been clearly established that the major histocompatibility (MHC) haplotype is a relative risk factor for ANKENT.…”

“…Doubly transgenic mice with hu-β2m in addition to HLA-B*2702 have higher cell-membrane expression of HLA-B2702, but no increased risk for ANKENT as compared with HLA-B*2702 singly trangenic littermates (Weinreich et al 1995a;Chopin et al 1996). This suggests that HLA-B*2702/mo-β2m heterodimers might be a relative risk factor, while HLA-B*2702/huβ2m heterodimers might be irrelevant in disease susceptibility.…”