Posted 23 January 2004

General Information

Transgene:

Heterozygous and homozygous mutant PS-1 (PS1-P264L) mice were cross-bred with mouse line overexpressing an APP695_swe transgene carrying the FAD-linked Swedish double mutation (Tg2576) or a mouse line carrying a targeted APP_swe double knock-in mutation and a "humanized" Aβ domain (APP_swe KI)

PS-1(P264L) and APP_swe

Phenotype

Neuropathological analysis:

Double cross mice have both PS-1 and APP mutation. Cultured neurons secrete Aβ42 at increased rate but Aβ40 secretion is reduced. The PS-1 knock-in mutation selectively increases Aβ42 levels in the mouse brain and accelerates the onset of amyloid deposition and its attendant reactive gliosis, even as a single mutant allele.

Behavioral: N/A

Availability

Contact Dorothy Flood at dflood@cephalon.com or Steve Trusko strusko@cephalon.com at Cephalon

Patents: None

Reference

Primary

Siman R, Reaume AG, Savage MJ, Trusko S, Lin YG, Scott RW, Flood DG. Presenilin-1 P264L knock-in mutation: differential effects on abeta production, amyloid deposition, and neuronal vulnerability. J Neurosci 2000 Dec 1;20(23):8717-26. Abstract.