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Strain Name:

B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J

Stock Number:

003378

Availability:

Repository-Cryopreserved


Price and Supply Information

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 SystemSee Colony Maintenance         (Female x Male)
Specieslaboratory mouse
Donating Investigator David Borchelt,   McKnight Brain Inst, Univ of Florida
GenerationF2N2+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

Alzheimer Disease 3
Alzheimer Disease 4
Alzheimer Disease; AD
Mammalian Phenotype Terms assigned by genotype

Tg(APP695)3Dbo/0 Tg(PSEN1)5Dbo/0

        involves: C3H/HeJ * C57BL/6J
  • nervous system phenotype
  • *normal* nervous system phenotype (MGI Ref ID J:100961)
    • no differences in neuron number in cingulate cortex relative to wild-type
    • abnormal neuron morphology (MGI Ref ID J:43788)
      • dystrophic neuritis associated with reactive gliosis in cortex and hippocampus
    • abnormal neuron physiology (MGI Ref ID J:100961)
      • neurons in cingulate cortex display 3-fold elevation in phosphorylated tumor suppressor protein (pRb) and activated caspase-3 relative to wild-type neurons
    • amyloid beta deposits (MGI Ref ID J:43788)
      • amyloid beta deposits found in cortex and hippocampus tissue from 9 and 12 month old mice and increase in number between 10 ans 12 months of age
      • amyloid beta peptides AB1-40 and AB1-42 are codeposited
      • ratio of amyloid beta peptide 40:42 is 1.75:1
      • exhibits a 50% increase in amyloid beta peptide 42
      • immunoreactive amyloid beta deposits are observed in the cingulate cortex in 12 month-old double transgenic mice; deposits are most evident in gray matter of cingulate and enthorhinal cortex, and to lesser extent in non-neuronal layers of the hippocampal formation
    • astrocytosis (MGI Ref ID J:43788)
      • associated with dystropic neuritis in cortex and hippocampus
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:43788)
    • amyloid beta deposits found in cortex and hippocampus tissue from 9 and 12 month old mice and increase in number between 10 ans 12 months of age
    • amyloid beta peptides AB1-40 and AB1-42 are codeposited
    • ratio of amyloid beta peptide 40:42 is 1.75:1
    • exhibits a 50% increase in amyloid beta peptide 42
    • immunoreactive amyloid beta deposits are observed in the cingulate cortex in 12 month-old double transgenic mice; deposits are most evident in gray matter of cingulate and enthorhinal cortex, and to lesser extent in non-neuronal layers of the hippocampal formation

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Tg(APP695)3Dbo/0 Tg(PSEN1)5Dbo/0

        B6.Cg-Tg(APP695)3Dbo Tg(PSEN1)5Dbo
  • nervous system phenotype
  • amyloid beta deposits (MGI Ref ID J:100956)
    • at 12 and 17 months of age, females have significantly more plaques in the hippocampus compared to males; plaque load increases dramatically with age in mice, particularly in females
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:100956)
    • at 12 and 17 months of age, females have significantly more plaques in the hippocampus compared to males; plaque load increases dramatically with age in mice, particularly in females

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(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, 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. [MGI Ref ID J:80882]

Control Information

  Control
   Noncarrier
   100010 B6C3F1/J
 
  Considerations for Choosing Controls
  Control Pricing Information for JAX® GEMM® Strains

Genotyping Protocols

Tg(APP)
Tg(PSEN1)

Colony Maintenance

Breeding & HusbandryThe 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)

View Strains carrying other alleles of APP695     (6 strains)

View Strains carrying other alleles of PSEN1     (5 strains)

View Strains carrying other alleles of Prnp     (16 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:

Neurobiology Research
Alzheimer's Disease (APP and PSEN1 mutants)
Alzheimer's Disease (Presenilin mutants)
Alzheimer's Disease (strains expressing mutant APP)

Tg(APP695)3Dbo related

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Alzheimer's Disease
Neurodegeneration

References

Selected Reference(s)

Borchelt 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]  [MGI Ref ID J:43788]

Additional References

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. The shipping destinations are:

*Pricing for Shipping Destination selected:

        USA, Canada and Mexico

Price(s) in US dollars ($)
Cryorecovery Fee $1900.00

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and 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.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

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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.
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