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.
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.
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
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.
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.
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