General Information

Transgene: Mouse APP genomic DNA, contained within universal targeting vector pPNTlox[2]

Mutation: Site-specific mutation of three codons in exon 16 of mouse (129/SV) APP sequence to (1) introduce the two Swedish familial AD mutations; and (2) "humanize" murine Aβ sequence by altering three amino acids

Mouse Strain: Mice generated from R1 line of embryonic stem cells

Phenotype

Neuropathological Analysis:

In brain, mutant mouse APP with humanized Aβ domain is expressed at levels comparable to mouse APP in wild type.

Amyloidogenic processing of the mutant mouse APP at the β-secretase site is enhanced.

"Human" Aβ found in mutant mice at levels nine-fold greater than that found in normal human brain.

Availability

Patents: None

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

Reference

Reaume AG, Howland DS, Trusko SP, Savage MJ, Lang DM, Greenberg BD, Siman R, Scott RW. Enhanced amyloidogenic processing of the β-amyloid precursor protien in gene-targeted mic bearing the Swedish familial Alzheimer's disease mutations and "humanized" Aβ sequence. J Biol Chem. 20 Sept 1996;271(38):23380-8. Abstract