title: Transgenic mice over-expressing carbonic anhydrase I showed aggravated joint inflammation and tissue destruction.
abstract: BACKGROUND
  Studies have demonstrated that carbonic anhydrase I (CA1) stimulates calcium salt precipitation and cell calcification, which is an essential step in new bone formation. Our study had reported that CA1 encoding gene has a strong association with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), two rheumatic diseases with abnormal new bone formation and bone resorption in joints. This study investigated the effect of CA1 on joint inflammation and tissue destruction in transgenic mice that over-express CA1 (CA1-Tg).
  
  
  METHODS
  CA1-Tg was generated with C57BL/6J mice by conventional methods. CA1-Tg was treated with collagen-II to induce arthritis (CIA). Wild-type mice, CA1-Tg treated with bovine serum albumin (BSA) and transgenic mice over-expressing PADI4 (PADI4-Tg), a gene known to be involved in rheumatoid arthritis, were used as controls. Histochemistry and X-ray radiographic assay were used to examine joint destruction. Western blotting and real time-PCR were used to examine CA1 expression.
  
  
  RESULTS
  CIA was observed in 60% of CA1-Tg, 20% of PADI4-Tg and 20% of wild-type mice after collagen injections. No CIA was found in CA1-Tg mice that received injections of BSA. The arthritic score was 5.5 ± 0.84 in the CA1-Tgs but the score was less than 2 in the injected wild-type mice and the PADI4-Tgs. The thickness of the hind paws in the CA1-Tgs was 3.46 ± 0.11 mm, which was thicker than that of PADI4-Tgs (2.23 ± 0.08 mm), wild-type mice (2.08 ± 0.06 mm) and BSA-treated CA1-Tgs (2.04 ± 0.07 mm). Histochemistry showed obvious inflammation, synovial hyperplasia and bone destruction in the joints of CA1-Tg that was not detected in PADI4-Tgs or wild-type mice. X-ray assays showed bone fusion in the paws and spines of CA1-Tg mice.
  
  
  CONCLUSIONS
  Over-expression of CA1 may aggravate joint inflammation and tissue destruction in the transgenic mice.
authors.affiliation: Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jingshi road 16766, Jinan, Shandong 250014, PR China.
authors.forename: Yabing
authors.initials: Y
authors.lastname: Zheng
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hengwei
authors.initials: H
authors.lastname: Xu
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Chang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control; D001175:Arthrography; D015153:Blotting, Western; D024401:Carbonic Anhydrase I / Q000235:genetics / Q000378:metabolism*; D024043:Collagen Type II; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D060888:Real-Time Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000008:administration & dosage; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D024043:Collagen Type II; D012710:Serum Albumin, Bovine; D006867:Hydrolases; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; C552151:peptidylarginine deiminase 4, mouse; D024401:Carbonic Anhydrase I