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Strain Name:

C3B6-Tg(APP695)3Dbo/J

Stock Number:

003375

Availability:

Repository-Cryopreserved


Price and Supply Information

General Terms and Conditions

Former Name      C57BL/6-TgN(Prn-APP695)3Dbo    (Changed: 15-DEC-04 )
Genes & Alleles   APP695;   Prnp;   Tg(APP695)3Dbo;


Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Strain
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Donating Investigator David Borchelt,   McKnight Brain Inst, Univ of Florida

Strain Description
These transgenic mice express the human amyloid precursor protein bearing the Swedish (K670N/M671L) mutation and develop amyloid deposits in brain tissue by 18-20 months of age. These mice provide a useful model for studying the underlying mechanism of amyloid deposition, a process implicated in Alzheimer's disease (AD).

Strain Development
Mouse pronuclei (B6C3H) were injected with a transgenic construct containing a cDNA encoding a chimeric amyloid beta (A4) precursor protein (APP695) regulated by the mouse prion promoter. The chimeric APP695 molecule was created by replacing sequences encoding the Abeta domain of the murine sequence with the cognate sequences of the human gene and mutations K595N and M596L (APP695 isoform numbering).

Related Disease (OMIM) Terms

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

Tg(APP695)3Dbo/0

        involves: C3H/HeJ * C57BL/6J
  • nervous system phenotype
  • *normal* nervous system phenotype (MGI Ref ID J:43788)
    • no immunoreactive amyloid beta deposits found in cortex or hippocampus from 12 month old mice as compared to double transgenic mice: Tg(APP695)3Dbo/0, Tg(PSEN1)5Dbo/0
    • amyloid beta deposits (MGI Ref ID J:43788)
      • amyloid beta deposits observed in cortex and hippocampus of 18 and 20 month old mice
      • ratio of amyloid beta peptide 40:42 is 3:1
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:43788)
    • amyloid beta deposits observed in cortex and hippocampus of 18 and 20 month old mice
    • ratio of amyloid beta peptide 40:42 is 3:1

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

Tg(APP695)3Dbo/0

        B6.C3-Tg(APP695)3Dbo
  • nervous system phenotype
  • amyloid beta deposits (MGI Ref ID J:109847)
    • in mice 26 months old, moderate levels of amyloid deposits in brains are observed in mice backcrossed 5-7 generations
    • mice 12-13 months old that have been backcrossed 10 generations have slightly higher accumulations than Tg(APP695)3Dbo mice
    • old (<24 months) animals backcrossed either 5-7 or 10 times to B6 have significantly higher levels of amyloid Abeta in their brains than adult (~9.6 months) or middle aged (13-15 months) animals
  • behavior/neurological phenotype
  • abnormal motor capabilities/coordination/movement (MGI Ref ID J:109847)
    • at 24 months, males display a mild deterioration of sensorimotor abilities
    • abnormal locomotor activity (MGI Ref ID J:109847)
      • in radial maze testing, male mutants backcrossed 5-7 generations show high motor reactivity compared to females or control animals, and entered the closest arm of the maze which prevented them from learning the task
    • increased startle reflex (MGI Ref ID J:109847)
      • mice backcrossed 10 generations have higher reactivity to acoustic stimuli compared to wild type
  • hearing/vestibular/ear phenotype
  • increased startle reflex (MGI Ref ID J:109847)
    • mice backcrossed 10 generations have higher reactivity to acoustic stimuli compared to wild type
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:109847)
    • in mice 26 months old, moderate levels of amyloid deposits in brains are observed in mice backcrossed 5-7 generations
    • mice 12-13 months old that have been backcrossed 10 generations have slightly higher accumulations than Tg(APP695)3Dbo mice
    • old (<24 months) animals backcrossed either 5-7 or 10 times to B6 have significantly higher levels of amyloid Abeta in their brains than adult (~9.6 months) or middle aged (13-15 months) animals

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]

Control Information

  Control
   Noncarrier
 
  Considerations for Choosing Controls
  Control Pricing Information for JAX® GEMM® Strains

Genotyping Protocols

Tg(APP)

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying   Tg(APP695)3Dbo allele
005866   B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J
003378   B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J
View Strains carrying   Tg(APP695)3Dbo     (2 strains)

View Strains carrying other alleles of APP695     (6 strains)

View Strains carrying other alleles of Prnp     (17 strains)

Additional Web Information

Genetic Quality Control Annual Report
JAX® NOTES, Summer 2004; 494. New Mouse Models for Alzheimer's Disease Research.
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 (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; Thinakaran G; Eckman CB; Lee MK; Davenport F; Ratovitsky T; Prada CM; Kim G; Seekins S; Yager D; Slunt HH; Wang R; Seeger M; Levey AI; Gandy SE; Copeland NG; Jenkins NA; Price DL; Younkin SG; Sisodia SS. 1996. Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 17(5):1005-13. [PubMed: 8938131]  [MGI Ref ID J:80882]

Additional References

Price and Supply Information

Strain Name: C3B6-Tg(APP695)3Dbo/J
Stock Number: 003375

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
Cryopreserved Embryos Fee $1600.00

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryopreserved Embryos
This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page.
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.
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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General Terms and Conditions

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For additional Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.

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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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