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Strain Detail Sheet

Strain Name:
B6J.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/Mmjax
Stock Number:
034833-JAX
Citation ID:
RRID:MMRRC_034833-JAX
Other Names:
This strain was formerly available as JAX Strain #005866. APPswe line C3-3 x PS1dE9 line S-9. The alleles follow dated nomenclature conventions and could also be referred to as Tg(Prnp-App*)3Dbo and Tg(Prnp-PSEN1*)S9Dbo.

Strain Information

Gene Details

App
Name: amyloid beta precursor protein
Synonyms: betaAPP, Abeta, protease nexin II, Adap, Cvap, appican, E030013M08Rik
Type: Gene
Species: Mouse
Chromosome: 16
NCBI: 11820
VEGA: 16
HGNC: HGNC:620
Homologene: 56379

Additional Resources
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APP
Name: amyloid beta precursor protein
Type: Gene
Species: Homo sapiens (human)
Chromosome: 21
Tg(APP695)3Dbo
Name: transgene insertion 3, David R Borchelt
Synonyms: APP695swe, Mo/HuAPPswe, line C3-3, APPswe, APP695
Type: Transgene
Species: Multi-species
Chromosome: unknown
Alteration at locus: Transgenic
PSEN1
Name: presenilin 1 (Alzheimer disease 3)
Type: Gene
Species: Homo sapiens (human)
Chromosome: 14
Alteration at locus: Transgenic
Tg(PSEN1dE9)S9Dbo
Name: transgene insertion S9, David R Borchelt
Synonyms: huPS1deltaE9, PS1 deltaE9, PS1deltaE9 (line S-9), PS1 transgene (line S-9), deltaE9, PS1-deltaE9, PS1dE9 transgene, line S-9
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic (random, gene disruption)
Genetic Alterations
The App transgene construct is composed of a cDNA encoding a chimeric APP protein regulated by the mouse prion promoter (Prnp). The chimeric App molecule was created by replacing sequences encoding the Abeta domain of a 695 amino acid isoform of the murine sequence with the cognate sequences of the human APP gene with variant K595N and M596L (found in familial Alzheimer's disease, also known as K670N/M671L or "Swedish mutation").

APP "Swedish Mutation" - K670N/M671L
  • Genbank RefSeq - mRNA: NM_001198823.1
  • Genbank RefSeq, protein: NP_001185752.1
  • Variant, nucleic acid level: c.2010G>T and c.2011A>C = c.2010_2011inv
  • Variant, amino acid level, predicted: p.Lys670_Met671delinsAsnLeu (K670N/M671L)
    Check this variant: LUMC Mutalyzer

The PSEN1 transgene construct is derived from the cDNA of the familial Alzheimer disease-(FAD-)associated deltaE9 variant of human presenilin 1, which has a splice acceptor mutation upstream of exon 9 that predicts a protein lacking amino acids 290-319. The mutant cDNA replaces the coding region of the mouse prion protein (Prnp) gene in a construct that contains ~6 kb of genomic DNA upstream of the primary PRP translation start site and includes the noncoding first exon and first intron and, following the inserted PSEN1 sequence, ~3 kb of 3' untranslated sequence
Genotype Determination

Strain Description

Phenotype
Homozygous: Not evaluated
Hemizygous: 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 months of age (PMID:12101040).
MeSH Terms
  • Acetylcholine/biosynthesis
  • Acetylcholine/genetics
  • Alzheimer Disease/genetics
  • Alzheimer Disease/metabolism
  • Alzheimer Disease/physiopathology
  • Amyloid beta-Peptides/biosynthesis
  • Amyloid beta-Peptides/genetics
  • Amyloid beta-Peptides/metabolism
  • Amyloid beta-Protein Precursor/biosynthesis
  • Amyloid beta-Protein Precursor/genetics
  • Animals
  • Female
  • Humans
  • Male
  • Maze Learning/physiology
  • Membrane Proteins/biosynthesis
  • Membrane Proteins/genetics
  • Memory Disorders/genetics
  • Memory Disorders/metabolism
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurotransmitter Agents/biosynthesis
  • Neurotransmitter Agents/genetics
  • Presenilin-1
  • Reaction Time/physiology
  • Somatostatin/biosynthesis
  • Somatostatin/genetics
  • Age of Onset
  • Alzheimer Disease/pathology
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Brain/metabolism
  • Brain/pathology
  • Cells, Cultured
  • Endopeptidases/genetics
  • Endopeptidases/metabolism
  • Membrane Proteins/metabolism
  • Mutation, Missense
  • Peptide Fragments/genetics
  • Peptide Fragments/metabolism
  • Amyloid beta-Protein Precursor/analysis
  • Astrocytes/chemistry
  • Brain Chemistry
  • Gene Expression
  • Genetic Vectors/genetics
  • Membrane Proteins/analysis
  • Mice, Transgenic/genetics
  • Myocardium/chemistry
  • Neurons/chemistry
  • Organ Specificity
  • Prions/genetics
  • RNA, Messenger/analysis
  • Amyloid beta-Protein Precursor/metabolism
  • Gene Transfer Techniques
  • Genes
  • Genetic Vectors
  • Immunoblotting
  • Mice/genetics
  • Polymerase Chain Reaction
  • Transgenes
Strain Development
Mutant amyloid precursor protein (APPswe) transgenic mice (line C3-3) express a chimeric mouse/human APP-695 with mutations linked to familial Alzheimer's 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 (C57BL/6J x C3H/HeJ)F2 background, the S-9 line was backcrossed to C57BL/6J for six generations. Both are under the control of the mouse prion protein (Prnp) 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 MMRRC.
Suggested Control Mice
Wild-type littermates

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.

Research Applications

  • Models for Human Disease
  • Neurobiology

Strain Origin

Donor
David Borchelt, Ph.D., University of Florida.
Primary Reference

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)

Colony and Husbandry Information

Special Considerations

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.

Health Status Report

Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-reports.

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email csmmrrc@jax.org.

Reproductive Statistics

Bred to Homozygosity
No

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Conditions of Distribution

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*		 Units Notes
034833-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
034833-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.