APP/PS1 are double transgenic mice expressing a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9), both directed to CNS neurons. Both mutations are associated with early-onset Alzheimer's disease. These mice may be useful in studying neurological disorders of the brain, specifically Alzheimer's disease, amyloid plaque formation and aging.
Mike Sasner, The Jackson Laboratory
Gareth Howell, JAX
APP/PS1 are double transgenic mice expressing a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9), both directed to CNS neurons. Both mutations are associated with early-onset Alzheimer's disease. The "humanized" Mo/HuAPP695swe transgene allows the mice to secrete a human A-beta peptide. Both the transgenic peptide and holoprotein can be detected by antibodies specific for human sequence within this region (Signet Laboratories' monoclonal 6E10 antibody). The included Swedish mutations (K595N/M596L) elevate the amount of A-beta produced from the transgene by favoring processing through the beta-secretase pathway. WSB.APP/PS1 female hemizygotes exhibit increased loss of cortical region and CA1 NEUN+DAPI+ (hippocampal) neurons, as well as impaired short-term memory, compared to controls. Cortical plaques are fewer in number compared to B6.APP/PS1 mice. WSB.APP/PS1 males exhibit a decreased number of hippocampal plaques (compared to B6.APP/PS1 controls), while WSB.APP/PS1 females do not. Hemizygotes are viable and fertile.
Homozygous viability/fertility has not been tested (May 2019). Of note, pregnant mutant female mice are removed from mating boxes and house individually due to increased pup mortality and given treats (BioServ Supreme) to discourage pup cannibalism.
APP/PS1 mice are also available on the PWK/PhJ (PWK.APP/PS1, Stock No. 025971) and CAST/EiJ (CAST.APP/PS1, Stock No. 025973) wild derived backgrounds.
B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax (Stock No. 34832-JAX) mice were backcrossed to WSB/EiJ (Stock No. 001145) for 12 generations.
To generate B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax (Stock No. 34832-JAX) two expression plasmids (Mo/HuAPP695swe and PS1-dE9) were designed to each be controlled by independent mouse prion protein (PrP) promoter elements, directing transgene expression predominantly to CNS neurons. The Mo/HuAPP695swe transgene expresses a "humanized" mouse amyloid beta (A4) precursor protein gene modified at three amino acids to reflect the human residues and further modified to contain the K595N/M596L (otherwise known as K670N/M671L) mutations linked to familial Alzheimers. The PS1-dE9 transgene expresses a mutant human presenilin 1 carrying the exon-9-deleted variant (PSEN1dE9) associated with familial Alzheimer's disease. These constructs were coinjected into B6C3HF2 pronuclei and insertion of the transgenes occured at a single locus. Founder line 85 was obtained and the resulting colony was maintained as a hemizygote by crossing transgenic mice to B6C3F1/J mice. Transgenic mice were then backcrossed to C57BL/6J for at least eight generations. The mice were then backcrossed to WSB/EiJ (Stock No. 001145) for 12 generations to produce this strain.
|Expressed Gene||APP, amyloid beta precursor protein, human|
|Expressed Gene||PSEN1, presenilin 1, human|
|Site of Expression|
|Allele Name||transgene insertion 85, David R Borchelt|
|Allele Type||Transgenic (Inserted expressed sequence, Humanized sequence)|
|Allele Synonym(s)||transgene insertion 85, David R Borchelt; Tg(APPswe,PSEN1dE9)85Dbo|
|Gene Symbol and Name||Tg(APPswe,PSEN1dE9)85Dbo, transgene insertion 85, David R Borchelt|
|Gene Synonym(s)||APPswe/PS1dE9; APdE9; APP/PS1; Mo/Hu APPswe PS1dE9|
|Promoter||Prn, prion protein readthrough transcript, mouse, laboratory|
|Expressed Gene||APP, amyloid beta precursor protein, human|
|Expressed Gene||PSEN1, presenilin 1, human|
|Strain of Origin||(C57BL/6 x C3H)F2|
|General Note||Mice carrying this double transgene develop beta-amyloid deposits in the brain by 6 to 7 months of age.|
|Molecular Note||Two transgenes inserted at a single locus in Chromosome 9 between Arpp21 and Pdcd6ip. Each transgene is controlled by the mouse prion promoter and contains a cDNA sequence. In one transgene the cDNA encodes a chimeric amyloid beta (A4) precursor protein (APPswe). In the second transgene the cDNA encodes the "DeltaE9" mutation of human presenilin 1. The DeltaE9 mutation of the human presenilin 1 gene is a deletion of exon 9 and corresponds to a form of early-onset Alzheimer's disease. The amyloid beta precursor protein coding sequences were altered by replacing mouse sequence encoding three amino acids of the A-beta domain with the human coding sequence for these residues. The chimeric amyloid beta (A4) precursor protein sequence was then further modified to encode the Swedish mutations K595N/M596L found in human. Both the transgenic peptide and holoprotein are detected by Signet Laboratories' monoclonal 6E10 antibody, which is specific for human sequence within this region. Human presenilin protein, which in high levels displaces detectable endogenous mouse protein, is immunodetected in the double transgenic mouse in whole brain protein homogenates. Human amyloid precursor protein is also immunodetected in these mice in whole brain protein homogenates. Transgene insertion occurred on Chr 9, causing a 1 bp duplication.|
|Mutations Made By|| |
Dr. David Borchelt, University of Florida
When maintaining a live colony, hemizygous mice may be bred to wildtype siblings, or to WSB/EiJ (Stock No. 001145). Homozygous viability/fertility has not been tested (June 2019).
When using the WSB.APP/PS1 mouse strain in a publication, please cite the originating article(s) and include JAX stock #025970 in your Materials and Methods section.
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
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