Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders.
Humans who have inherited the human class I major histocompatibility allele HLA-B27 have a markedly increased risk of developing the multi-organ system diseases termed spondyloarthropathies. To investigate the role of B27 in these disorders, we introduced the B27 and human beta 2-microglobulin genes into rats, a species known to be quite susceptible to experimentally induced inflammatory disease. Rats from one transgenic line spontaneously developed inflammatory disease involving the gastrointestinal tract, peripheral and vertebral joints, male genital tract, skin, nails, and heart. This pattern of organ system involvement showed a striking resemblance to the B27-associated human disorders. These results establish that B27 plays a central role in the pathogenesis of the multi-organ system processes of the spondyloarthropathies. Elucidation of the role of B27 should be facilitated by this transgenic model.
Hammer
R E
RE
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235.
Maika
S D
SD
Richardson
J A
JA
Tang
J P
JP
Taurog
J D
JD
D000818:Animals; D015152:Blotting, Northern; D004064:Digestive System / Q000473:pathology; D005805:Genes, MHC Class I; D005821:Genetic Techniques; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007592:Joint Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007596:Joints / Q000473:pathology; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values; D012867:Skin / Q000473:pathology; D014158:Transcription, Genetic; D001613:beta 2-Microglobulin / Q000235:genetics*
D015796:HLA-B27 Antigen; D012333:RNA, Messenger; D001613:beta 2-Microglobulin