Use of genetically altered mice to study the role of serum amyloid P component in amyloid deposition.
A precise role for serum amyloid P component (SAP), a common component of all known types of amyloid fibrils, in amyloid deposition in vivo is not known. Thus we investigated the relationship between SAP and amyloid deposition, using the transgenic mouse model of familial amyloidotic polyneuropathy (FAP). Because high serum levels of mouse endogenous or human SAP did not affect human transthyretin-derived amyloid deporsition in the transgenic mouse model of FAP, we approached this question by analyzing the induction of experimental AA amyloidosis in SAP-deficient and wild-type mice. Our experiments presented compelling evidence that, although not essential in the deposition of AA amyloid, SAP significantly accelerates the reaction. We then examined the persistence of splenic AA amyloid fibrils in SAP-deficient and wild-type mice to assess potential ways of treating individuals with amyloidosis. Our results indicated that lack of SAP in AA amyloid deposits does not enhance regression of the deposits in vivo and suggested that dissociation of bound SAP from AA amyloid deposits would not significantly accelerate regression of the deposits in vivo.
Maeda
Shuichiro
S
First Department of Biochemistry, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan. smaeda@res.yamanashi-med.ac.jp
D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011228:Prealbumin / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D008070:Lipopolysaccharides; D011228:Prealbumin; D000685:Serum Amyloid A Protein; D000683:Serum Amyloid P-Component