Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice.
Overexpression of Alzheimer amyloid precursor protein (APP) produces dramatically different phenotypes in transgenic mice depending on the genetic background. For example, concentrations of APP that produce amyloid plaques in outbred transgenic lines are lethal for inbred FVB/N or C57BL/6J mice. Expression of SOD1 transgenes is protective, suggesting involvement of oxidative damage in premature death, but ablation of Apoe had no significant effect. In contrast, FGF2 transgene overexpression enhances the lethal effects of APP. Differential survival does not appear to reflect genetic differences in APP processing, but rather host responses to APP or its derivatives.
Carlson
G A
GA
McLaughlin Research Institute, Great Falls, MT 59405, USA. gac@po.mri.montana.edu
Borchelt
D R
DR
Dake
A
A
Turner
S
S
Danielson
V
V
Coffin
J D
JD
Eckman
C
C
Meiners
J
J
Nilsen
S P
SP
Younkin
S G
SG
Hsiao
K K
KK
D000483:Alleles; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D005804:Genes, Lethal; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D016222:Fibroblast Growth Factor 2; D013482:Superoxide Dismutase