Phenotype Homozygous phenotype: Not evaluated
Hemizygous phenotype: Double transgenic mice are viable and fertile. At 6 months of age, double-transgenic mice show visible amyloid plaque deposition but are indistinguishable from nontransgenic animals in all cognitive measures. By 18 months, amyloid deposits were much higher in APPswe/PS1dE9 mice with statistically significant but mild decreases in cholinergic markers (cortex and hippocampus) and somatostatin levels (cortex). Performance of older double-transgenic mice is impaired in all cognitive tasks, and deficits in episodic-like memory tasks correlate with total amyloid-beta peptide loads in the brain. Mutant mice, hemizygous for each transgene, and on the C57BL/6J background (N6), have altered EEG (decreased cortical theta activity and increased beta and gamma activity). EEG differences are detected as early as 7 month of age (Wang et al. Brain Res 2002).
Mammalian Phenotype Terms:(provided by MGI)Extend all MPTs assigned by genotype
The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Background Not Specified
nervous system phenotype
abnormal amacrine cell morphology (MGI Ref ID J:139070)
distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining
abnormal microglial cell morphology (MGI Ref ID J:139070)
increase in microglial cell activity in retina is observed in 12-15 month old transgenics
microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control
microglia density, but not cell body size, is increased in transgenics
at 7 months of age, mice exhibit amyloid plaques in the hippocampus and cortex (MGI Ref ID J:104236)
develops diffuse, compact, birefringent congophilic plaques in cortex and hippocampus (MGI Ref ID J:87691)
ratio of amyloid beta peptide 40:42 is 0.75:1 (MGI Ref ID J:87691)
150% increase in amyloid beta peptide 42 (MGI Ref ID J:87691)
Founder genetic background: C3B6
Strain genetic background: B6.Cg
Strain Development: Mutant amyloid precursor protein (APPswe) transgenic mice (line C3-3) express a chimeric mouse/human APP-695 with mutations linked to familial Alzheimers disease (KM 593/594 NL). The C3-3 line was backcrossed to C57BL/6J mice for 10 generations. Presenilin 1 (PSEN1) transgenic mice (line S-9) express human PSEN1 carrying the exon-9-deleted variant (PSEN1dE9) associated with familial Alzheimer's disease. Originally created on a hybrid strain background (C3H/HeJ;C57BL/6J), the S-9 line was backcrossed to C57BL/6J for six generations. Both are under the control of the mouse prion protein (PrP) promoter, directing transgene expression predominantly to CNS neurons. APPswe/PS1dE9 double transgenic mice were produced by mating APP-695 line C3-3 males to PS1dE9 line S-9 females, and then backcrossing double transgenic males to C57BL/6J mice for >10 generations before arriving at The Repository.
Suggested Control Mice: Wild-ype littermates
Models for Human Disease
David Borchelt, Ph.D., McKnight Brain Institute, University of Florida
Savonenko A; Xu GM; Melnikova T; Morton JL; Gonzales V; Wong MP; Price DL; Tang F; Markowska AL; Borchelt DR, Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities., Neurobiol Dis 2005 Apr;18(3):602-17
(Medline PMID: 15755686)
Jankowsky JL; Fadale DJ; Anderson J; Xu GM; Gonzales V; Jenkins NA; Copeland NG; Lee MK; Younkin LH; Wagner SL; Younkin SG; Borchelt DR, Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase., Hum Mol Genet 2004 Jan 15;13(2):159-70
(Medline PMID: 14645205 )
Borchelt DR; Davis J; Fischer M; Lee MK; Slunt HH; Ratovitsky T; Regard J; Copeland NG; Jenkins NA; Sisodia SS; Price DL, A vector for expressing foreign genes in the brains and hearts of transgenic mice., Genet Anal 1996 Dec;13(6):159-63
(Medline PMID: 9117892)
Jankowsky JL; Slunt HH; Ratovitski T; Jenkins NA; Copeland NG; Borchelt DR, Co-expression of multiple transgenes in mouse CNS: a comparison of strategies., Biomol Eng 2001 Jun;17(6):157-65
(Medline PMID: 11337275)
When maintaining a live colony, The Jackson Laboratory will maintain this line by mating (APP695/0, +/+) females with (+/+, PSEN1/0) males (or reciprocal). The transgenes are not linked (only 1 in 4 pups is a double transgenic); and the integration site is unknown.
For more information about this colony's health status contact email@example.com
Order Request Information
Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at firstname.lastname@example.org for more details.
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Distribution of this strain requires submission of the MMRRC Conditions of Use (COU).
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