General Information

Mouse construction: The mouse line was derived using a two-step mutagenesis strategy.  A PS-1 targeting vector was constructed consisting of a mouse genomic fragment spanning exon 8 and including portions of the surrounding introns and bearing base changes in the coding region at codons P264L and 265. Codon 265 is a silent substitution that creates a novel AflII restriction site. 

The targeting vector was introduced via electroporation into the R1 line of the ES cells (129 mouse strain), and homologous recombinants were identified by a positive-negative drug selection scheme. 

Mouse background: Heterozygous PS-1 P264L/wt and homozygous PS-1 P264L/P264L lines were established in the CD-1 outbred background.

Phenotype

Neuropathological analysis:

Neither the basal level of morphological apoptosis nor the response to three different apoptogenic agents was altered significantly in primary cortical neurons by the PS-1 P264L knock-in mutation.

Staurosporine and Ab1-42 induce apoptosis, and neither the dose dependence nor maximal extent of cell death is altered by the PS-1 knock-in mutation.  Glutamate-induced neuronal necrosis is unaffected by the mutation.

Behavioral: N/A

Availability

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

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.