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| This strain is now distributed by the Mutant Mouse Regional Resource Center. Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for ordering information and strain details on B6.129S4-Tg(APPSwLon)96Btla/Mmjax
MMRRC Stock Number 034837. As a designated MMRRC center, The Jackson Laboratory will continue to distribute these mice at the same high health and quality standards but ordering is exclusively provided through the MMRRC. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Former Names B6.129S4-Tg(APPSwLon)96Btla/J (Changed: 11-AUG-11 ) Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N12+F1pN1
Generation DefinitionsDonating 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 (B6.129-Tg(APPSw)40Btla/Mmjax). 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 MMRRC at The Jackson Laboratory.
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (107 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
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Alzheimer Disease; AD
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Cerebral Amyloid Angiopathy, App-Related (APP)
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
- no Alzheimer's disease pathology is observed at 2 years of age in homozygotes (MGI Ref ID J:58050)
- amyloid beta deposits
- 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 (MGI Ref ID J:42613)
- hemizygous mice have 2- to 3-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes (MGI Ref ID J:58050)
- other phenotype
- amyloid beta deposits
- 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 (MGI Ref ID J:42613)
- hemizygous mice have 2- to 3-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes (MGI Ref ID J:58050)
Tg(APPSwLon)96Btla/Tg(APPSwLon)96Btla
involves: 129S4/SvJae
- nervous system phenotype
- *normal* nervous system phenotype
- no Alzheimer's disease pathology is observed at 2 years of age in homozygotes (MGI Ref ID J:58050)
- amyloid beta deposits
- homzygous mice have 4- to 6-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes (MGI Ref ID J:58050)
- other phenotype
- amyloid beta deposits
- homzygous mice have 4- to 6-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes (MGI Ref ID J:58050)
This mouse can be used to support research in many areas including:
APP relatedNeurobiology Research
Alzheimer's Disease
strains expressing mutant APP
Neurodegeneration
Research Tools
Neurobiology Research
Neurobiology Research
Alzheimer's Disease
Neurodegeneration
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(APPSwLon)96Btla | ||
|---|---|---|---|
| Allele Name | transgene insertion 96, Bruce Lamb | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | APPK670N/M671L and APPV717Im; J1.96; K670N/M671L + V717I; | ||
| Mutation Made By | Bruce Lamb, The Cleveland Clinic Foundation | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/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 provided by MGI
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 relatedLamb 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
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, mice are bred by homozygous intercross.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
This strain is currently Transferred.
General Supply Notes
- 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.Ordering Information
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