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Strain Name:

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

Stock Number:

006406

Availability:

Repository- Live

Price and Supply Information

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Genes & Alleles   APP;   Tg(APPSwLon)96Btla;

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 SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Bruce Lamb,   The Cleveland Clinic Foundation
GenerationN12+F2 (30-APR-08)

Strain 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 wildtype 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).

Strain 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.

Related Disease (OMIM) Terms

Alzheimer Disease; AD
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

Gene & Allele Details

Allele Symbol Tg(APPSwLon)96Btla
Allele Name transgene insertion 96, Bruce Lamb
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]

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for JAX® GEMM® Strains

Genotyping Protocols

Tg(APP) QPCR
Tg(APPSw)40Btla

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, mice are bred by homozygous intercross.
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying other alleles of APP     (15 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:

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Alzheimer's Disease (strains expressing mutant APP)
Alzheimer's Disease
Neurodegeneration

Research Tools
Neurobiology Research

APP related

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Alzheimer's Disease
Neurodegeneration

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

Price and Supply Information

Strain Name: B6.129S4-Tg(APPSwLon)96Btla/J
Stock Number: 006406

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 ($)Genotype(s) Provided
Individual Mouse Price $203.80Homozygous for Tg(APPSwLon)96Btla
Pair $407.60Homozygous for Tg(APPSwLon)96Btla x Homozygous for Tg(APPSwLon)96Btla

Supply Details

Standard SupplyRepository-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.
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 1-800-422-6423.
Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.
View Control Pricing Information for JAX® Strains.

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.

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.
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