Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice

George A. Carlson, David R. Borchelt, Angela Dake, Sherry Turner, Valerie Danielson, J. Douglas Coffin, Chris Eckman, James Meiners, Steven P. Nilsen, Steven G. Younkin, Karen K. Hsiao

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1951-1959
Number of pages9
JournalHuman molecular genetics
Volume6
Issue number11
DOIs
StatePublished - Oct 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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