High levels of circulating beta-amyloid peptide do not cause cerebral beta-amyloidosis in transgenic mice.
We have established transgenic mice that constitutively overproduce the signal sequence and the 99-amino-acid carboxyl-terminal region of the human beta-amyloid precursor protein. The transgenic mice strongly expressed the transgene in multiple tissues under the control of a cytomegalovirus enhancer/chick beta-actin promoter. There were exceptionally high levels of beta-amyloid peptides in the plasma (approximately 17 times or more compared with the human plasma level). Although some transgenic mice from one founder line developed amyloidosis in the intestine, no neuropathology was found in transgenic mice up to age 29 months. Given the absence of cerebral beta-amyloidosis despite extremely high levels of circulating beta-amyloid peptides in the transgenic mice, the results suggest that local cerebral metabolism of beta-amyloid precursor protein may play a predominant role in cerebral beta-amyloidosis in transgenic mice. Such transgenic mice may be useful for the investigation of the etiology of the disease and for the establishment of therapeutic strategies.
Fukuchi
K
K
Department of Pathology, University of Washington, Seattle, Washington, USA.
Ho
L
L
Younkin
S G
SG
Kunkel
D D
DD
Ogburn
C E
CE
LeBoeuf
R C
RC
Furlong
C E
CE
Deeb
S S
SS
Nochlin
D
D
Wegiel
J
J
Wisniewski
H M
HM
Martin
G M
GM
D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000502:physiology; D000686:Amyloidosis / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000737:chemistry* / Q000473:pathology; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000737:chemistry; D009693:Nucleic Acid Hybridization; D010446:Peptide Fragments / Q000032:analysis* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012333:RNA, Messenger