SERUM AMYLOID-P COMPONENT ENHANCES INDUCTION OF MURINE AMYLOIDOSIS

Serum amyloid P component (SAP), a common component of all known types of amyloid fibrils, protects amyloid fibrils from proteolysis in vitr o. It is therefore speculated to contribute to the deposition of amylo id fibrils in various types of amyloidoses. However, a role for SAP in amyloid deposition is not yet known. To investigate the relationship between SAP and amyloid deposition, we used gene targeting techniques to generate a unique strain of mice carrying a null mutation at the sa p locus. The resultant SAP-deficient mice displayed no obvious phenoty pic abnormalities. We asked whether experimental amyloid A (AA) amyloi dosis could be induced in the SAP-deficient mice. The wild-type and SA P-deficient mice did not differ in their synthesis of serum amyloid A, the precursor protein of AA amyloid fibril, in response to acute infl ammation. The induction of AA amyloidosis, however, was significantly retarded in the SAP-deficient mice relative to wild-type mice. Our exp eriments present, for the first time, compelling evidence that, althou gh not essential in the deposition of AA amyloid, SAP significantly ac celerates this reaction. Thus, SAP enhances the induction of murine am yloidosis and may play an important role in the pathogenesis of human amyloidoses, including Alzheimer's disease.