Long-term dialysis is very often complicated with amyloid deposits, predominantly in aricular synovial membranes. The amyloid deposition is a serious complication of dialysis as it excessively deteriorates the quality of life of long-term dialysis patients. A major component of amyloid deposits was identified as beta2-microglobulin (beta2-m) having a molecular weight of 11,800 daltons.
The details of amyloidogenesis of this type of amyloid remain unknown. At present, a variety of the factors contributing to the pathogenesis have been proposed. They include calcium, amyloid P component, glycosaminoglycans, and collagens. Furthermore, macrophages, monokines, proteases, free radicals, and apolipoprotein E are also suggested to play roles in amyloid fibril formation. Although the mechanism is probably multifactorial, the retention of beta2-m, that is a precursor protein of this type of amyloid, is considered to be a principal requirement for the trigger of this processes.
To analyze the mechanisms of amyloid deposition in dialysis-related amyloidosis, we have tried to develop a model mouse for the amyloidosis. Transgenic mice by microinjecting human beta2-m cDNA ligated with a MML virus DNA as a promoter were developed.
Synovia and other organs were obtained from mice sacrificed at the age of between 3 months and 6 months, and examined histopathologically and immunohistochemically.
There was no Congo red positive lesion in any organs and no significant staining with beta2-m antibody except liver.
Studies are still in progress with long-term follow-up observation.