Strain Name: |
B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J |
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Stock Number: |
005866 |
Availability: | Repository- Live |
Price and Supply Information | |
General Terms and Conditions |
| Genes & Alleles | APP695; PSEN1; Prnp; Tg(APP695)3Dbo; Tg(PSEN1dE9)S9Dbo; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Transgenic Mating System See Colony Maintenance (Female x Male) Species laboratory mouse Donating Investigator David Borchelt, McKnight Brain Inst, Univ of Florida Generation [N7p]+N3F3 (04-DEC-07) Strain Description
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.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 Jackson Laboratory.
Related Disease (OMIM) Terms |
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Tg(APP695)3Dbo | ||
|---|---|---|---|
| Allele Name | transgene insertion 3, David R Borchelt | ||
| Common Name(s) | APP695; APP695swe; APPswe; Mo/HuAPPswe; line C3-3; | ||
| Mutation Made By | David Borchelt, McKnight Brain Inst, Univ of Florida | ||
| Strain of Origin | (C57BL/6J x C3H/HeJ)F2 | ||
| Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera | ||
| Promoter | Prnp, prion protein, mouse, laboratory | ||
| General Note |
Three transgenic lines were generated and designated by the authors lines Q2-2, E1-2 (Tg(Prnp-App/APPswe)E1-2Dbo) and C3-3. This line was generated from foundernumber C3-3. Transgenic mice develop amyloid deposits in brain tissue by 18-20 months of age. Transgenic mice that are also transgenic for Tg(PSEN1)5Dboexpress both human presenilin 1 (A246E variant) and a chimeric amyloid precursor protein (APPSwe) under direction of the mouse prion protein promoter. Elevated levels of the AB1-42(43) peptide are detected in brain homogenates. By nine months of age, histological examination of brain tissue from these mice reveals numerous amyloid deposits resembling those observed in the brains of patients with Alzheimer's disease (AD). The number of amyloid deposits increases dramatically between the ages of 10 and 12 months. | ||
| Molecular Note | The transgene is composed of a cDNA encoding a chimeric APP protein regulated by the mouse prion promoter. 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 gene (mutations K595N, M596L). The human mutations are found in familial Alzheimer's disease. Transgene expression was observed in the brain and heart by Western blot analysis using a monoclonal antibody recognizing the human Abeta region. [MGI Ref ID J:80782] | ||
| Allele Symbol | Tg(PSEN1dE9)S9Dbo | ||
| Allele Name | transgene insertion S9, David R Borchelt | ||
| Common Name(s) | PS1 transgene (line S-9); PS1-deltaE9; PS1dE9 transgene; PS1deltaE9 (line S-9); deltaE9; huPS1deltaE9; line S-9; | ||
| Mutation Made By | David Borchelt, McKnight Brain Inst, Univ of Florida | ||
| Strain of Origin | (C57BL/6J x C3H/HeJ)F2 | ||
| Expressed Gene | PSEN1, presenilin 1, human | ||
| General Note |
The deltaE9 PSEN1 protein variant fails to undergo endoproteolysis in cultured lymphoblasts from an affected human carrier and instead accumulates as the full-length, 40 kDa mutant protein (J:34323). Similarly, immunoblotting of of cortical and hippocampal extracts from transgenic mice under conditions that distinguish mouse and human full-length PSEN1 and their endoproteolytic derivatives demonstrates failure of thetransgenic protein to undergo endoproteolysis. (J:104147) The amount of full-length mutant human PSEN1 in brains of deltaE9 PSEN1 transgenic mice exceeds by ~60% the cumulative amount of the full-length human PSEN1 and its N-terminal derivative in brains of transgenic mice expressing wild type human PSEN1. (J:104147) | ||
| Molecular Note | The coding sequence of the transgene 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 results in a protein lacking amino acids 290-319. The mutant cDNA replaces the coding region of the mouse prion protein (Prp) 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; this construct has been shown to drive expression in both neurons and glial cells of the central nervous system (CNS). [MGI Ref ID J:104147] [MGI Ref ID J:34323] [MGI Ref ID J:80782] | ||
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for JAX® GEMM® Strains | ||
Genotyping Protocols
Tg(APP)
Tg(PSEN1)
Colony Maintenance
| Breeding & Husbandry | 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. The Jackson Laboratory will distribute mice with the following genotypes: (PARENT 1) hemizygous APP695, wildtype PSEN1; (PARENT 2) wildtype APP695, hemizygous PSEN1; and (OFFSPRING) double hemizygotes. Control mice can be generated from this breeding pair or investigators can consider C57BL/6J (Stock 000664). While the donating investigator warns that transgenic females can exhibit suboptimal mothering of litters, no such complications have been observed in our colonies to date at The Jackson Laboratory (Jun 2006). Homozygosity may result in sterile males and reduced viability of females, and should be avoided for breeding stocks. |
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| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
Strains carrying Tg(APP695)3Dbo allele
003378 B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J 003375 C3B6-Tg(APP695)3Dbo/J View Strains carrying Tg(APP695)3Dbo (2 strains)
Additional Web Information
Congenic Nomenclature
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Animal Health Reports
Room Number AX11
Research Applications
This mouse can be used to support research in many areas including:
Tg(APP695)3Dbo relatedNeurobiology Research
Alzheimer's Disease (APP and PSEN1 mutants)
Alzheimer's Disease (Presenilin mutants)
Alzheimer's Disease (strains expressing mutant APP)
Behavioral and Learning Defects
Mouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
Neurodegeneration
References
Selected Reference(s)
Additional ReferencesSavonenko A; Xu GM; Melnikova T; Morton JL; Gonzales V; Wong MP; Price DL; Tang F; Markowska AL; Borchelt DR. 2005. Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. Neurobiol Dis 18(3):602-17. [PubMed: 15755686] [MGI Ref ID J:104236]
Price and Supply Information
| Strain Name: | B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J |
| Stock Number: | 005866 |
Price Details
IMPORTANT NOTE: Prices are based on shipping destination. The shipping destinations are:
- USA, Canada and Mexico
- International
*Pricing for Shipping Destination selected:
International
| Price(s) in US dollars ($) | Genotype(s) Provided | ||||
|---|---|---|---|---|---|
| Individual Mouse Price | $301.60 | Hemizygous for Tg(APP695)3Dbo, Hemizygous for Tg(PSEN1dE9)S9Dbo | |||
| Individual Mouse Price | $301.60 | Hemizygous for Tg(APP695)3Dbo, Noncarrier | |||
| Individual Mouse Price | $301.60 | Noncarrier, Hemizygous for Tg(PSEN1dE9)S9Dbo | |||
| Pair | $603.20 | Noncarrier, Hemizygous for Tg(PSEN1dE9)S9Dbo x Hemizygous for Tg(APP695)3Dbo, Noncarrier | |||
Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
Histology and Tissue Collection Services are available for all JAX® Mice strains. For more information, please contact Customer Service at orderquest@jax.org or 1-207-288-5845. Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. View Control Pricing Information for JAX® Strains. |
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
For additional Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.
The Jackson Laboratory's Genotype Promise
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering and Purchasing Information
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