Transgenic mice expressing bovine GH develop arthritic disorder and self-antibodies.
We observed disability of movement in 6-month-old transgenic mice expressing the fusion gene coding for the bovine GH (bGH) under the transcriptional control of phosphoenolpyruvate carboxykinase promoter (PEPCK-bGH). Histological study of the knee joint showed altered synovial and tibial articular cartilage tissues. In the cartilage the following observations were made: (i) generalized loss of the normal zonal structure and presence of clefts, and (ii) profound alterations in chondrocyte growth/differentiation processes consistent with hypertrophy. The synovial tissue showed a reduced number of adipocytes, and a significant thickening of synovial lining tissue and pannus. These findings indicate that transgenic mice suffer damage to diarthritic joints with osteoarthritic appearance. As changes in synovial membrane in osteoarthritis are almost indistinguishable from those seen in inflammatory arthritis, we determined the potential correlation with an immunological disorder. Serological determination of self-antibodies measured as a function of age and sex showed anti-nuclear, anti-single-stranded DNA, anti-double-stranded DNA and anti-70K antibodies, and an altered immunoglobulin typing. These results suggest that transgenic mice expressing bGH develop an arthritic process which is correlated with an immune disorder. The results also indicate that these mice are a suitable animal model to study the specific role of GH-driven processes in immune cells and arthritis.
Ogueta
S
S
Departamento de Biología Molecular, Centro de Biología Molecular-Severo Ochoa, Facultad de Ciencias (UAM-CSIC), Cantoblanco, 28049 Madrid, Spain.
Olazabal
I
I
Santos
I
I
Delgado-Baeza
E
E
García-Ruiz
J P
JP
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D002417:Cattle; D004277:DNA, Single-Stranded / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics* / Q000276:immunology; D015151:Immunoblotting / Q000379:methods; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D011233:Precipitin Tests / Q000379:methods; D013583:Synovial Membrane / Q000473:pathology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D004277:DNA, Single-Stranded; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D013006:Growth Hormone