Mutant and native human beta-amyloid precursor proteins in transgenic mouse brain.
Human beta-amyloid precursor protein (beta APP) has been targeted to transgenic neurons using synapsin I promoter-based chimeric transgenes. Native human beta APP was introduced as well as beta APP containing mutations genetically linked to familial Alzheimer's disease (AD) and to hereditary cerebral hemorrhage with amyloidosis-Dutch type. In mouse brain, human beta APP RNA was up to 60% as abundant as total endogenous beta APP RNA. Human beta APP gene expression was most abundant in the CA subfields of the hippocampus and in the piriform cortex. Correct processing of human beta APP at the beta-secretase cleavage site was demonstrated in transgenic mouse brains. Despite a 40% increase in total beta APP immunoreactivity in lines expressing mutant human beta APP, no evidence of amyloid deposition was found in brains of mice up to 14 months in age. Higher levels of mutant human beta APP, increased age, or other factors may be necessary to elicit beta-amyloid-related neuropathologies in the rodent brain.
Howland
D S
DS
Cephalon Inc., West Chester, PA 19380, USA.
Savage
M J
MJ
Huntress
F A
FA
Wallace
R E
RE
Schwartz
D A
DA
Loh
T
T
Melloni
R H
RH
DeGennaro
L J
LJ
Greenberg
B D
BD
Siman
R
R
D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D012313:RNA / Q000378:metabolism; D016704:Synapsins / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D016704:Synapsins; D012313:RNA