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Posted 1 April 2005
Transgene: Tg mice were produced by pronuclear injection of fertilized eggs of C57Bl/6J × DBA/2J (B6D2) F1 hybrids. P117L FAD (Polish) mutant cDNAs were cloned into a neuron-specific enolase (NSE) expression vector.
Mutation: P117L
Promoter: Neuron-specific enolase (NSE) promoter
Mouse Strain: Mixed C57Bl/6 and DBA/2J background. All studies were performed using the hemizygous offspring of transgenic animals mated to B6D2 F1 hybrids with nontransgenic littermates utilized as controls.
Neuropathological Analysis:
Line 13 expresses the hPS1 2-3X the level of the endogenous mPS1. PS1P117L FAD mutant impairs new neuron production in adult hippocampus by decreasing neural progenitor survival. BrdU labeling and IHC showed that the human transgenic proteins are not expressed in neural progenitor cells in the hippocampus as would be expected of an NSE-driven transgene.P117L tg animals do not exhibit plaques or diffuse amyloid deposits at 2-3 months. However, they do overproduce the long 1-42 form of Aß.
Gregory A. Elder
Department of Psychiatry
Mount Sinai School of Medicine
New York, NY 10029
Email: gregory.elder@mssm.edu
Patents: None
Wen, P.H., Shao, X., Shao, Z., Hof, P.R., Wisniewski, T., Kelley, K., Friedrich Jr., V.L., Ho, L., Pasinetti, G.M., Shioi, J., Robakis, N.K. and Elder, G.A. Overexpression of wild type but not an FAD mutant presenilin-1 promotes neurogenesis in the hippocampus of adult mice. Neurobiol. Dis. 10:18-19, 2002. ">Abstract
Wen PH, Hof PR, Chen X, Gluck K, Austin G, Younkin SG, Younkin LH, DeGasperi R, Gama Sosa MA, Robakis NK, Haroutunian V, Elder GA. The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in the hippocampus of adult mice. Exp Neurol. 188(2):224-37, 2004. Abstract
Wen PH, Friedrich Jr VL, Shioi J, Robakis, NK, Elder, GA. Presenilin-1 is expressed in neural progenitor cells in the hippocampus of adult mice. Neurosci. Lett. 318, pp. 53-56, 2002. Abstract
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