Neurodegeneration and gliosis in transgenic mice overexpressing acarboxy-terminal fragment of Alzheimer amyloid-beta protein precursor
M. Sato
Bok Engelsk 1997
| Utgitt | 1997
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| Omfang | Side 296- 307
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| Opplysninger | In order to study the properties of beta-amyloid in vivo, wegenerated a total of 28 transgenic founder mice that harbored thegene for the 17-amino acid signal sequence and the 99-amino acidcarboxy-terminal fragment (CTF) of the human amyloid-beta proteinprecursor (beta APP) linked to the cytomegalovirus enhancer andchicken beta-actin promoter. Two of these founders, termed 0304 and0809, exhibited decreased behavioral activity with gliosis andneurodegeneration in the hippocampus at 2.5 and 9 months of age. Bothmice had also decreased levels of synaptophysin, a presynapticmarker, but no evidence for beta-amyloid deposition in their brains.Neurodegeneration in the hippocampus was transmitted to the offspringof mouse 0304, although the frequency was low (5 of 44 mice examined)and the time of onset of the disorder was rather later than that inthe founder mouse. This is probably due to reduced levels of thetransgene-derived products in the offspring of mouse 0304. The 0809line failed to produce its offspring. The other remaining transgenicfounders appeared normal and had lesser amounts of the CTF mRNA andprotein in their brains than did 0304 and 0809 founders, though somemice died in earlier stages or exhibited hydrocephalus. Thesefindings suggest that overexpression of the CTF of human beta APP hasthe potential to elicit neurodegeneration in vivo without appreciableproduction of beta-amyloid fibrils.
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| Emner |
