ABNORMAL ACCUMULATION OF APO-CERULOPLASMIN IN A RAT MODEL OF WILSONS-DISEASE

We examined the mechanism of decrease in serum ceruloplasmin (Cp) in L EC rats, an animal model of Wilson's disease. Northern blot analysis s howed that the level of Cp mRNA in the liver of LEC rats was similar t o that in control LEA rats. Moreover the serum level of Cp in LEC rats , determined by ELISA, was 70% of that in LEA rats, but its p-phenylen ediamine oxidase activity was significantly decreased. Serum Cp was de tected as two bands by polyacrylamide gel electrophoresis and immunobl ot analysis. Cp in the band with higher mobility had ferroxidase activ ity and was the predominant form in LEA rats, whereas that in the band of lower mobility was inactive and was the major form in LEC rats. Di alysis of serum against sodium cyanate to remove copper from Cp result ed in disappearance of the form of Cp of higher mobility with increase in the slower migrating form. These results demonstrate that the fast er and slower migrating forms of Cp are a holo-Cp and apo-Cp, respecti vely, and that LEC rats accumulate apo-Cp in their serum. A disturbanc e of copper binding to apo-Cp may be responsible for pathogenesis in L EC rats.