Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene.
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.
Botto
M
M
Rheumatology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Hawkins
P N
PN
Bickerstaff
M C
MC
Herbert
J
J
Bygrave
A E
AE
McBride
A
A
Hutchinson
W L
WL
Tennent
G A
GA
Walport
M J
MJ
Pepys
M B
MB
D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000139:chemically induced / Q000235:genetics; D000818:Animals; D002364:Caseins / Q000633:toxicity; D004195:Disease Models, Animal; D017353:Gene Deletion; D006023:Glycoproteins / Q000633:toxicity; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000683:Serum Amyloid P-Component / Q000235:genetics*; D012835:Silver Nitrate / Q000633:toxicity
D000682:Amyloid; D002364:Caseins; D006023:Glycoproteins; D000683:Serum Amyloid P-Component; C046748:amyloid enhancing factor; D012835:Silver Nitrate