Kininogen deficiency in the rat.
The Brown Norway Katholiek (B/N-Ka) strain rat is the only animal strain that demonstrates deficiency in plasma HMW- and LMW-kininogens with a low level of prekallikrein. We developed an RIA for rat HMW-kininogen, LMW-kininogen, and T-kininogen, and using them measured these proteins in B/N-Ka and normal strain (B/N-Ki) rats. Plasma level of immunoreactive as well as kinin-releasing HMW-kininogen and LMW-kininogen in B/N-Ka rats was either around 3% of their levels in the normal B/N-Ki rats. The cause of the plasma deficiency of kininogens in the B/N-Ka strain was examined by 35S-methionine uptake of primary cultures of hepatocytes from the B/N-Ki and B/N-Ka strains. The results indicated that the kininogens were synthesized in the B/N-Ka liver but not secreted into the medium. Northern blot analysis of poly A(+)RNA extracted from the livers of both strains demonstrated that the band corresponding to mRNA of HMW-kininogen was present in the mRNA from B/N-Ka liver as well as in that from the B/N-Ki one. The band was similar in size and intensity in both cases. This result confirmed the data that immunoreactive HMW-kininogen was found in the liver of B/N-Ka rats (12). Thus, the cause of plasma deficiency of HMW-kininogen in the mutant appears to be secretory defect in nature. The B/N-Ka rats showed less reactivity to the inflammatory stimulus, such as carrageenin or kaolin, but the strain expressed almost the same response as normal rats to phorbol ester (PMA) or zymosan for pleurisy induction. These results indicate that kinin may play an important role in exudation in carrageenin- and kaolin-induced edema but not in that induced by PMA or zymosan. The deficient rat strain could be useful for differentiation of the inflammatory model which shows involvement of the kinin system.
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007704:Kininogens / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D010998:Pleurisy / Q000209:etiology; D011061:Poly A / Q000235:genetics / Q000378:metabolism; D011288:Prekallikrein / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D011914:Rats, Inbred BN; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley
D007704:Kininogens; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D011288:Prekallikrein