Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene

被引:214
作者
Botto, M
Hawkins, PN
Bickerstaff, MCM
Herbert, J
Bygrave, AE
McBride, A
Hutchinson, WL
Tennent, GA
Walport, MJ
Pepys, MB
机构
[1] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,IMMUNOL MED UNIT,LONDON W12 0NN,ENGLAND
[2] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,RHEUMATOL UNIT,LONDON W12 0NN,ENGLAND
[3] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,RADIOL SCI UNIT,LONDON W12 0NN,ENGLAND
关键词
D O I
10.1038/nm0897-855
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The tissue amyloid deposits that characterize systemic amyloidosis, Alzheimer's disease and the transmissible spongiform encephalopathies always contain serum amyloid P component (SAP) bound to the amyloid fibrils. We have previously proposed that this normal plasma protein may contribute to amyloidogenesis by stabilizing the deposits. Here we show that the induction of reactive amyloidosis is retarded in mice with targeted deletion of the SAP gene. This first demonstration of the participation of SAP in pathogenesis of amyloidosis in vivo confirms that inhibition of SAP binding to amyloid fibrils is an attractive therapeutic target in a range of serious human diseases.
引用
收藏
页码:855 / 859
页数:5
相关论文
共 41 条
[1]  
AXELRAD MA, 1982, LAB INVEST, V47, P139
[2]  
BALTZ ML, 1980, CLIN EXP IMMUNOL, V39, P355
[3]   KINETICS OF SERUM AMYLOID PROTEIN-A IN CASEIN-INDUCED MURINE AMYLOIDOSIS [J].
BENSON, MD ;
SCHEINBERG, MA ;
SHIRAHAMA, T ;
CATHCART, ES ;
SKINNER, M .
JOURNAL OF CLINICAL INVESTIGATION, 1977, 59 (03) :412-417
[4]   Synchrotron X-ray studies suggest that the core of the transthyretin amyloid fibril is a continuous beta-sheet helix [J].
Blake, C ;
Serpell, L .
STRUCTURE, 1996, 4 (08) :989-998
[5]   Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis [J].
Booth, DR ;
Sunde, M ;
Bellotti, V ;
Robinson, CV ;
Hutchinson, WL ;
Fraser, PE ;
Hawkins, PN ;
Dobson, CM ;
Radford, SE ;
Blake, CCF ;
Pepys, MB .
NATURE, 1997, 385 (6619) :787-793
[6]   IMAGING OF EXPERIMENTAL AMYLOIDOSIS WITH I-131-LABELED SERUM AMYLOID P COMPONENT [J].
CASPI, D ;
ZALZMAN, S ;
BARATZ, M ;
TEITELBAUM, Z ;
YARON, M ;
PRAS, M ;
BALTZ, ML ;
PEPYS, MB .
ARTHRITIS AND RHEUMATISM, 1987, 30 (11) :1303-1306
[7]  
CATHCART ES, 1967, P SOC EXP BIOL MED, V125, P1123
[8]   AMYLOIDOSIS AND FEMALE PROTEIN IN THE SYRIAN-HAMSTER - CONCURRENT REGULATION BY SEX-HORMONES [J].
COE, JE ;
ROSS, MJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 171 (04) :1257-1267
[9]   UNALTERED SUSCEPTIBILITY TO BSE IN TRANSGENIC MICE EXPRESSING HUMAN PRION PROTEIN [J].
COLLINGE, J ;
PALMER, MS ;
SIDLE, KCL ;
HILL, AF ;
GOWLAND, I ;
MEADS, J ;
ASANTE, E ;
BRADLEY, R ;
DOEY, LJ ;
LANTOS, PL .
NATURE, 1995, 378 (6559) :779-783
[10]  
CORIA F, 1988, LAB INVEST, V58, P454