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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 D2.129(B6)-Tg(APPSw)40Btla/Mmjax
MMRRC Stock Number 034839. 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. | ||||||||||||||||||||||
| These R1.40 transgenic mice express all mRNA and protein isoforms of the human amyloid beta (A4) precursor protein APP containing the Familial Alzheimer's Disease (FAD) Swedish mutation K670N/M671L, and may be useful in studying the pathogenesis of Familial Alzheimer's Disease and possible therapeutic treatments. | ||||||||||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Former Names D2.129(B6)-Tg(APPSw)40Btla/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 N28+F2N2F1pN1
Generation DefinitionsDonating Investigator Bruce Lamb, The Cleveland Clinic Foundation
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (108 strains)
006409 129S1.129(Cg)-Tg(APPSw)40Btla/Mmjax 006555 A.129(B6)-Tg(APPSw)40Btla/Mmjax 005300 B6.129-Tg(APPSw)40Btla/Mmjax
006409 129S1.129(Cg)-Tg(APPSw)40Btla/Mmjax 006555 A.129(B6)-Tg(APPSw)40Btla/Mmjax 005300 B6.129-Tg(APPSw)40Btla/Mmjax
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
assigned by genotype
Tg(APPSw)40Btla/Tg(APPSw)40Btla
D2.129-Tg(APPSw)40Btla
- nervous system phenotype
- *normal* nervous system phenotype
- no amyloid beta deposits are observed in 13.5 month-old mice (MGI Ref ID J:86629)
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(APPSw)40Btla/0
involves: 129S1/Sv * 129X1/SvJ
- nervous system phenotype
- amyloid beta deposits
- mice have higher levels of total A-beta protein and the cleaved A-beta 1-42(43) peptide than Tg(APP)8.9Btla mice, but levels are lower than those in Tg(APPSwLon)96Btla mice (MGI Ref ID J:42613)
- mice have 7- to 8-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes (MGI Ref ID J:58050)
- diffuse amyloid beta deposits are detected in the hippocampus and frontal cortex at 24-26 months of age (MGI Ref ID J:58050)
- other phenotype
- amyloid beta deposits
- mice have higher levels of total A-beta protein and the cleaved A-beta 1-42(43) peptide than Tg(APP)8.9Btla mice, but levels are lower than those in Tg(APPSwLon)96Btla mice (MGI Ref ID J:42613)
- mice have 7- to 8-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes (MGI Ref ID J:58050)
- diffuse amyloid beta deposits are detected in the hippocampus and frontal cortex at 24-26 months of age (MGI Ref ID J:58050)
Tg(APPSw)40Btla/Tg(APPSw)40Btla
involves: 129S1/Sv * 129X1/SvJ
- nervous system phenotype
- amyloid beta deposits
- homozygous mice have 15- to 20-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes (MGI Ref ID J:58050)
- extensive fibrillar amyloid beta deposits are detected in the hippocampus and frontal, cingulate and parietal cortex at 14-15 months of age (MGI Ref ID J:58050)
- other phenotype
- amyloid beta deposits
- homozygous mice have 15- to 20-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes (MGI Ref ID J:58050)
- extensive fibrillar amyloid beta deposits are detected in the hippocampus and frontal, cingulate and parietal cortex at 14-15 months of age (MGI Ref ID J:58050)
Tg(APPSw)40Btla/Tg(APPSw)40Btla
B6.129-Tg(APPSw)40Btla
- nervous system phenotype
- amyloid beta deposits
- all animals show amyloid beta (Abeta) deposits in the parietal cortex at 13.5 months of age, but no animals have deposits at 5 months (MGI Ref ID J:86629)
- other phenotype
- amyloid beta deposits
- all animals show amyloid beta (Abeta) deposits in the parietal cortex at 13.5 months of age, but no animals have deposits at 5 months (MGI Ref ID J:86629)
This mouse can be used to support research in many areas including:APP related
Mouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
Neurodegeneration
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(APPSw)40Btla | ||
|---|---|---|---|
| Allele Name | transgene insertion 40, Bruce Lamb | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | APPK670/M671; APPK670N/M671L; R1.40; R1.40-YAC; | ||
| Mutation Made By | Bruce Lamb, The Cleveland Clinic Foundation | ||
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| ES Cell Line Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| Expressed Gene | APP, amyloid beta (A4) precursor protein, human | ||
| Promoter | APP, amyloid beta (A4) precursor protein, human | ||
| Molecular Note | The transgenic insertion comprises four to eight copies of a 650-kb YAC containing the entire 400-kb human amyloid precursor protein gene with the Swiss familial Alzheimer disease (FAD) mutation and approximately 250 kb of flanking human DNA. The double mutation (K670N/M671N) comprises a G-to-A transition converting the lysine codon at position 670 to an asparagine codon and an A-to-C transversion replacing the methionine at amino acid 671 with leucine. RT-PCR and western blot analysis revealed that hemizygous transgenic mice express all major human APP mRNA and protein isoforms in brain, in parallel with the corresponding mouse versions, at approximately three times the levels of the latter. Total brain levels of the Alzheimer disease- associated 42-amino acid amyloid-beta peptide detected by ELISA are 7-8-fold and 15-20-fold higher, respectively, in mice hemizygous and homozygous for the mutant gene than in hemizygotes for the wildtype human gene. Levels of a cell-associated, beta-secretase-generated 13.5 kDa C-terminal peptide containing the amyloid beta domain and of soluble amyloid beta peptides are significantly elevated in brains of mice with the mutant, versus wildtype, transgene, while alpha-secretase products are diminished. [MGI Ref ID J:42613] [MGI Ref ID J:58050] [MGI Ref ID J:73622] | ||
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)
Lehman EJ; Kulnane LS; Gao Y; Petriello MC; Pimpis KM; Younkin L; Dolios G; Wang R; Younkin SG; Lamb BT. 2003. Genetic background regulates beta-amyloid precursor protein processing and beta-amyloid deposition in the mouse. Hum Mol Genet 12(22):2949-56. [PubMed: 14506131] [MGI Ref ID J:86629]
Additional References
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]
Tg(APPSw)40Btla relatedChiocco MJ; Lamb BT. 2007. Spatial and temporal control of age-related APP processing in genomic-based beta-secretase transgenic mice. Neurobiol Aging 28(1):75-84. [PubMed: 16387391] [MGI Ref ID J:117963]
Ghosal K; Stathopoulos A; Pimplikar SW. 2010. APP intracellular domain impairs adult neurogenesis in transgenic mice by inducing neuroinflammation. PLoS One 5(7):e11866. [PubMed: 20689579] [MGI Ref ID J:163067]
Kulnane LS; Lamb BT. 2001. Neuropathological characterization of mutant amyloid precursor protein yeast artificial chromosome transgenic mice. Neurobiol Dis 8(6):982-92. [PubMed: 11741394] [MGI Ref ID J:73622]
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]
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]
Ryman D; Gao Y; Lamb BT. 2008. Genetic loci modulating amyloid-beta levels in a mouse model of Alzheimer's disease. Neurobiol Aging 29(8):1190-8. [PubMed: 17400334] [MGI Ref ID J:140915]
Salehi A; Delcroix JD; Belichenko PV; Zhan K; Wu C; Valletta JS; Takimoto-Kimura R; Kleschevnikov AM; Sambamurti K; Chung PP; Xia W; Villar A; Campbell WA; Kulnane LS; Nixon RA; Lamb BT; Epstein CJ; Stokin GB; Goldstein LS; Mobley WC. 2006. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51(1):29-42. [PubMed: 16815330] [MGI Ref ID J:122937]
Varvel NH; Bhaskar K; Kounnas MZ; Wagner SL; Yang Y; Lamb BT; Herrup K. 2009. NSAIDs prevent, but do not reverse, neuronal cell cycle reentry in a mouse model of Alzheimer disease. J Clin Invest 119(12):3692-702. [PubMed: 19907078] [MGI Ref ID J:155100]
Varvel NH; Bhaskar K; Patil AR; Pimplikar SW; Herrup K; Lamb BT. 2008. Abeta oligomers induce neuronal cell cycle events in Alzheimer's disease. J Neurosci 28(43):10786-93. [PubMed: 18945886] [MGI Ref ID J:144634]
Vogt DL; Thomas D; Galvan V; Bredesen DE; Lamb BT; Pimplikar SW. 2009. Abnormal neuronal networks and seizure susceptibility in mice overexpressing the APP intracellular domain. Neurobiol Aging :. [PubMed: 19828212] [MGI Ref ID J:169998]
Yang Y; Varvel NH; Lamb BT; Herrup K. 2006. Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models. J Neurosci 26(3):775-84. [PubMed: 16421297] [MGI Ref ID J:104514]
Health & husbandry
Health & Colony Maintenance Information
Currently there is no information available for this strain. This may be due to the supply level of this strain.
Purchasing information
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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