Strain Name:

B6.129S4-Tg(APPSwLon)96Btla/J

Stock Number:

006406

Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN12+F1pN1
 
Donating Investigator Bruce Lamb,   The Cleveland Clinic Foundation

Description
Mice hemizygous for this "K670N/M671L + V717I" mutant APP YAC transgene are viable and fertile. RT-PCR analysis shows hemizygous mice express the mutant human APP mRNA at levels similar to endogenous mouse in brain and peripheral tissues. Further, transcript levels of the most common alternative splice variants (encoding human APP-695, -751 and -770) parallel the endogenous mouse gene expression. The levels of total amyloid-beta and longer amyloid-beta peptides (species terminating at amino acids 42/43) are elevated compared to wild-type mice, but not to the extent as observed in a similar strain carrying only the APP (K670N/M671L) mutant transgene (see Stock No. 005300). These mice may be useful in studies of the pathogenesis of Familial Alzheimer?s Disease, specifically focusing on the importance of processing at the gamma-secretase site to elevate levels of amyloid-beta 1-42(43).

Development
A 650 kb YAC transgene containing the entire human amyloid beta (A4) precursor protein (APP) gene, and approximately 250 kb of flanking sequence, was altered to include the Swiss mutation (K670N/M671L) and the London mutation (V717I) associated with Familial Alzheimer's Disease (FAD). This construct was injected into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Founder animals (line J1.96) were found to contain a single copy of this mutant human APP YAC transgene. These mutants were backcrossed to C57BL/6 for at least 11 generations prior to arrival at The Jackson Laboratory.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of APP     (16 strains)

Additional Web Information

Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

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

Tg(APPSwLon)96Btla/0

        involves: 129S4/SvJae
  • nervous system phenotype
  • *normal* nervous system phenotype (MGI Ref ID J:58050)
    • no Alzheimer's disease pathology is observed at 2 years of age in homozygotes
    • amyloid beta deposits (MGI Ref ID J:42613)
      • mice have much higher levels of total A-beta protein and the cleaved A-beta 1-42(43) peptide than Tg(APPSw)40Btla mutant mice or Tg(APP)8.9Btla mice
      • hemizygous mice have 2- to 3-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:42613)
    • mice have much higher levels of total A-beta protein and the cleaved A-beta 1-42(43) peptide than Tg(APPSw)40Btla mutant mice or Tg(APP)8.9Btla mice
    • hemizygous mice have 2- to 3-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes

Tg(APPSwLon)96Btla/Tg(APPSwLon)96Btla

        involves: 129S4/SvJae
  • nervous system phenotype
  • *normal* nervous system phenotype (MGI Ref ID J:58050)
    • no Alzheimer's disease pathology is observed at 2 years of age in homozygotes
    • amyloid beta deposits (MGI Ref ID J:58050)
      • homzygous mice have 4- to 6-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:58050)
    • homzygous mice have 4- to 6-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Alzheimer's Disease
      strains expressing mutant APP
Neurodegeneration

Research Tools
Neurobiology Research

APP related

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Alzheimer's Disease
Neurodegeneration

Genes & Alleles

Gene & Allele Information

 
Allele Symbol Tg(APPSwLon)96Btla
Allele Name transgene insertion 96, Bruce Lamb
Allele Type Transgenic (random, expressed)
Common Name(s) APP and APP; J1.96; K670N/M671L + V717I;
Mutation Made By Bruce Lamb,   The Cleveland Clinic Foundation
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Expressed Gene APP, amyloid beta (A4) precursor protein, human
Promoter APP, amyloid beta (A4) precursor protein, human
General Note The transgene construct was injected into embryonic stem (ES) cells.
Molecular Note A 650 kb YAC transgene containing the entire human amyloid beta (A4) precursor protein gene and approximately 250 kb of flanking sequence was altered to include the Familial Alzheimer's Disease- (FAD-) associated "Swedish" double mutation, APPK670N/M671L, and the "London" mutation, APPV717I. RT-PCR analysis shows hemizygous mice express the mutant human and endogenous mouse APP mRNA at similar levels in brain and peripheral tissues; levels of the most common alternative splice variants (encoding human APP-695, -751 and -770) parallel those of the endogenous mouse transcripts. Levels of total amyloid-beta and of longer amyloid-beta peptides (species terminating at amino acids 42/43) are higher than in wildtype mice, but not as high as in a similar strain carrying only the APPK670N/M671L "Swedish" mutant transgene. [MGI Ref ID J:42613]
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(APP), QPCR
Tg(APPSw)40Btla, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Lamb BT; Call LM; Slunt HH; Bardel KA; Lawler AM; Eckman CB; Younkin SG; Holtz G; Wagner SL; Price DL; Sisodia SS; Gearhart JD. 1997. Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice. Hum Mol Genet 6(9):1535-41. [PubMed: 9285791]  [MGI Ref ID J:42613]

Additional References

Tg(APPSwLon)96Btla related

Lamb BA; Bardel KA; Kulnane LS; Anderson JJ; Holtz G; Wagner SL; Sisodia SS; Hoeger EJ. 1999. Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice. Nat Neurosci 2(8):695-7. [PubMed: 10412057]  [MGI Ref ID J:58050]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, mice are bred by homozygous intercross.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Price (US dollars $)
Cryorecovery Fee $1900.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Price (US dollars $)
Cryorecovery Fee $2470.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Additional Supply Details

Supply Details

Standard SupplyCryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
  International - Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


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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.
Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


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

Contact information

General inquiries

Contracts Administration

phone:207-288-6470
fax:207-288-6655

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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