Strain Name: |
B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J |
|---|---|
Stock Number: |
003378 |
Availability: | Repository-Cryopreserved |
General Terms and Conditions |
| Former Name |
B6C3F1-TgN(Prn-APP695)3Dbo TgN(Prn-PSEN1)5Dbo (Changed: 15-DEC-04
) |
| Genes & Alleles | APP695; PSEN1; Prnp; Tg(APP695)3Dbo; Tg(PSEN1)5Dbo; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Mutant Strain Additional information on JAX® GEMM® Strains. 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 F2N2+N1p Strain Description
These transgenic mice express human presenilin 1 (A246E variant) and a chimeric amyloid precursor protein (APPSwe). The mouse prion protein promoter directs expression of both transgenes. Elevated levels of the AB1-42(43) peptide is detected in brain homogenates. By nine months of age, histological examination of brain tissue 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. These mice provide a useful model for studying the underlying mechanism of amyloid deposition, a process implicated in AD.Strain Development
Mouse pronuclei (B6C3H) were injected with an expression plasmid containing a mouse prion promoter and a cDNA encoding human presenilin 1 bearing the A246E substitution (line N-5). Another subset of mouse pronuclei (B6C3H) were injected with an expression plasmid containing a cDNA encoding a chimeric amyloid beta (A4) precursor protein, also regulated by the mouse prion promoter (line C3-3). The chimeric APP molecule was created by replacing sequences encoding the Abeta domain of the murine sequence with the cognate sequences of the human gene (mutations K595N, M596L). The two transgenic lines were subsequently mated to generate the double transgenic.
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. [J:80782] | ||
| Allele Symbol | Tg(PSEN1)5Dbo | ||
| Allele Name | transgene insertion 5, David R Borchelt | ||
| Common Name(s) | Hu PS1-A246E; PS1 A246E; PS1-A246E; PS1A246E; | ||
| Mutation Made By | David Borchelt, McKnight Brain Inst, Univ of Florida | ||
| Expressed Gene | PSEN1, presenilin 1 (Alzheimer disease 3), human | ||
| Promoter | Prnp, prion protein, mouse, laboratory | ||
| General Note |
This line was generated from founder number N-5. Transgenic mice that are also transgenic for Tg(APP695)3Dboexpress 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 numerousamyloid 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 consists of a mouse prion promoter and a cDNA encoding human presenilin 1 bearing the A246E substitution found in familial Alzheimer's disease (FAD). Transgene expression was verified by Northern and Western blot analysis of brain extracts derived from transgenic animals. [J:80882] | ||
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100010 B6C3F1/J | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Tg(APP695)
Tg(PSEN1)
Colony Maintenance
| Breeding & Husbandry | The strain originated on a mixed B6;C3H background. The investigator maintains the line by mating double transgenics to C3B6F1 mice. The double transgenics are hemizygous; they are not linked (only 1 in 4 pups is a double transgenic); and the integration site is unknown. Reproduction is excellent. TJL maintains this line by mating (APP695/0, +/+) x (+/+, PSEN1/0) (or reciprocal) to distribute mice APP695/+, PSEN1/+. Expected coat colors: agouti, black. TJL will supply 1) hemizygous APP695, wildtype PSEN1; 2) wildtype APP695, hemizygous PSEN1; and 3) double hemizygotes. Breeder pairs will be the hemizygous APP695, wildtype PSEN1 and the wildtype APP695, hemizygous PSEN1 from the colony (and the reciprocal). Control mice can be generated from this breeding pair. Alternatively, investigators can consider B6C3F1/J (Stock 100010). |
|---|
Related Strains
Strains carrying Tg(APP695)3Dbo allele
005866 B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J 003375 C3B6-Tg(APP695)3Dbo/J View Strains carrying Tg(APP695)3Dbo (2 strains)
Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
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)
Mouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
Neurodegeneration
References
Selected Reference(s)
Additional ReferencesBorchelt DR; Ratovitski T; van Lare J; Lee MK; Gonzales V; Jenkins NA; Copeland NG; Price DL; Sisodia SS. 1997. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron 19(4):939-45. [PubMed: 9354339] [J:43788]
Price and Supply Information
| Strain Name: | B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J |
| Stock Number: | 003378 |
Price Details
IMPORTANT NOTE: Prices are based on shipping destination. To view prices, select your shipping destination.
*NO Shipping Destination selected!
Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to the Supply Notes for further information. |
|---|---|
| Supply Notes |
Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. |
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
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form