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 vitro. It is therefore speculated to contribute to the deposition of amyloid 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 sap locus. The resultant SAP-deficient mice displayed no obvious phenotypic abnormalities. We asked whether experimental amyloid A (AA) amyloidosis could be induced in the SAP-deficient mice. The wild-type and SAP-deficient mice did not differ in their synthesis of serum amyloid A, the precursor protein of AA amyloid fibril, in response to acute inflammation. The induction of AA amyloidosis, however, was significantly retarded in the SAP-deficient mice relative to wild-type mice. Our experiments present, for the first time, compelling evidence that, although not essential in the deposition of AA amyloid, SAP significantly accelerates this reaction. Thus, SAP enhances the induction of murine amyloidosis and may play an important role in the pathogenesis of human amyloidoses, including Alzheimer's disease.
Togashi
S
S
First Department of Biochemistry, Yamanashi Medical University, Japan.
Lim
S K
SK
Kawano
H
H
Ito
S
S
Ishihara
T
T
Okada
Y
Y
Nakano
S
S
Kinoshita
T
T
Horie
K
K
Episkopou
V
V
Gottesman
M E
ME
Costantini
F
F
Shimada
K
K
Maeda
S
S
D000210:Acute-Phase Reaction / Q000097:blood; D000686:Amyloidosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D002460:Cell Line; D017353:Gene Deletion; D006801:Humans; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011498:Protein Precursors / Q000097:blood; D000685:Serum Amyloid A Protein / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000009:adverse effects* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells
D001053:Apolipoproteins; D011498:Protein Precursors; D000685:Serum Amyloid A Protein; D000683:Serum Amyloid P-Component