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.
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.
Contact Dorothy Flood at firstname.lastname@example.org
or Steve Trusko email@example.com
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.