Strain Name: |
D2.129(B6)-Tg(APPSw)40Btla/J |
|---|---|
Stock Number: |
006472 |
Availability: | Repository- Live |
Price and Supply Information | |
General Terms and Conditions |
| Strain Common Names | D2-R1.40; |
| Genes & Alleles | APP; Tg(APPSw)40Btla; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Stock Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Transgenic Mating System Noncarrier x Hemizygote (Female x Male) Species laboratory mouse Donating Investigator Bruce Lamb, The Cleveland Clinic Foundation Generation N28 (08-JAN-08) Strain Description
These 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. Transgene expression (mRNA and full-length protein) is 2 to 3 fold the endogenous mouse App expression level in the hemizygous state in brain tissue as revealed by RT-PCR and Western Blot analysis. Transgene expression pattern mimics endogenous mouse gene expression patterns. The donating investigator reports increased mortality in young homozygous animals (higher incidence in females). This mutant mouse strain represents a model that may be useful in studies of the pathogenesis of Familial Alzheimer's Disease and possible therapeutic treatments.In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. A publication (Lehman et al. 2003 Hum Mol Genet 12:2949) compares the well characterized B6-R1.40 strain (C57BL/6J congenic, see Stock No. 005300) with two additional congenic strains, D2-R1.40 (DBA/2J congenic, see Stock No. 006472) and 129S1-R1.40 (129S1/SvImJ congenic, see Stock No. 006409). While these three congenic strains have similar levels of holo-APP in brain tissue, the levels of brain APP C-terminal fragments (CTFs) vary depending upon genetic background. Brain and plasma levels of amyloid beta-40 and -42 are variable as well (B6-R1.40 > 129S1-R1.40 > D2-R1.40). In addition, the congenic strains exhibited dramatic alterations in the age of onset of amyloid beta deposition; in contrast to 14 month old homozygous B6-R1.40 mice, homozygous D2-R1.40 and 129S1-R1.40 mice do not develop amyloid beta deposits in the parietal or frontal cortex even by 20 months of age. The donating investigator further reports that the A-R1.40 strain (A/J congenic, see Stock No. 006555) exhibits levels of amyloid beta comparable to the B6-R1.40 strain, but with later onset. Therefore, APP processing and amyloid beta metabolism and deposition are modified by the genetic background. While the 129S1-R1.40 strain can be easily maintained as homozygotes, the donating investigator reports increased mortality in young homozygotes on the other genetic backgrounds, with D2-R1.40 and A-R1.40 more severely affected than B6-R1.40.
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 associated with Familial Alzheimer's Disease (FAD). This transgene was injected into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Founder animals (line R1.40) were established and bred to C57BL/6J for an unknown number of generations. After this, transgenic mice were bred to DBA/2J (Stock No. 000671) for at least 26 generations prior to arrival at The Jackson Laboratory. This transgene inserted on Chromosome 13.
Related Disease (OMIM) Terms |
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Tg(APPSw)40Btla | ||
|---|---|---|---|
| Allele Name | transgene insertion 40, Bruce Lamb | ||
| 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] | ||
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000671 DBA/2J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for JAX® GEMM® Strains | ||
Genotyping Protocols
Tg(APPSw)40Btla
Colony Maintenance
| Breeding & Husbandry | When maintaining a live colony, transgenic carriers may be bred together, to wildtype siblings, or to DBA/2J inbred mice. Because of the increased mortality in young homozygous animals (higher incidence in females), maintaining the colony by breeding homozygotes together is only recommended when sufficient colony size is permitted. |
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| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
Strains carrying Tg(APPSw)40Btla allele
006409 129S1.Cg-Tg(APPSw)40Btla/J 006555 A.129(B6)-Tg(APPSw)40Btla/J 005300 B6.129-Tg(APPSw)40Btla/J View Strains carrying Tg(APPSw)40Btla (3 strains)
005301 B6.129S2-Tg(APP)8.9Btla/J 006406 B6.129S4-Tg(APPSwLon)96Btla/J 005864 B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/J 004662 B6.Cg-Tg(PDGFB-APP)5Lms/J 004661 B6.Cg-Tg(PDGFB-APPSwInd)20Lms/1J 006293 B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2J 006006 B6.Cg-Tg(Prnp-APP)A-2Dbo/J 006005 B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/J 007049 B6.Cg-Tg(tetO-APPSwInd)885Dbo/J 004462 B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J 006004 B6C3-Tg(tetO-APPSwInd)885Dbo/J 007027 C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/J
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 AX12
Research Applications
This mouse can be used to support research in many areas including:
APP relatedMouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease (strains expressing mutant APP)
Alzheimer's Disease
Neurodegeneration
Research Tools
Neurobiology Research
Mouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
Neurodegeneration
References
Selected Reference(s)
Additional ReferencesLehman 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]
Price and Supply Information
| Strain Name: | D2.129(B6)-Tg(APPSw)40Btla/J |
| Stock Number: | 006472 |
Price Details
IMPORTANT NOTE: Prices are based on shipping destination. The shipping destinations are:
- USA, Canada and Mexico
- International
*Pricing for Shipping Destination selected:
USA, Canada and Mexico
| Price(s) in US dollars ($) | Genotype(s) Provided | ||||
|---|---|---|---|---|---|
| Individual Mouse Price | $236.40 | Hemizygous for Tg(APPSw)40Btla | |||
| Pair | $288.65 | Hemizygous for Tg(APPSw)40Btla x Noncarrier | |||
| Pair | $288.65 | Noncarrier x Hemizygous for Tg(APPSw)40Btla | |||
Supply Details
| Standard Supply | Repository-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. |
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| 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. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. View Control Pricing Information for JAX® Strains. |
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
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.Ordering and Purchasing Information
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