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Strain Name:

B6.129-Tg(APPSw)40Btla/J

Stock Number:

005300

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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 Strain
Type JAX® GEMM® Strain - Transgenic
Mating SystemHemizygote x Noncarrier         (Female x Male)
Specieslaboratory mouse
Donating Investigator Bruce Lamb,   The Cleveland Clinic Foundation
GenerationN22+F2 (08-DEC-07)

Strain Description
These transgenic mice express all mRNA and protein isoforms of the human amyloid beta (A4) precursor protein APP containing the Familial Alzheimer 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. Levels of the beta- secretase generated human APP derivative, C-terminal 13.5kDA fragment, are elevated in brain tissue. ELISA enzyme-linked immunosorbent assay (ELISA) analysis of brain homogenates show a significant increase in total amyloid-beta peptides and 42 amino acid length amyloid beta peptides. By 14 months of age, homozygous mice develop both parenchymal and vascular amyloid beta deposits, which first appear in the frontal cortex and then spread into the hippocampus. 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.

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 APPK670N/M671L associated with Familial Alzheimer's Disease. This transgene was injected into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Founder animals (line R1.40) were backcrossed to C57BL/6J for 21 generations prior to arrival at The Jackson Laboratory.

Related Disease (OMIM) Terms

Alzheimer Disease; AD
Mammalian Phenotype Terms assigned by genotype

Tg(APPSw)40Btla/Tg(APPSw)40Btla

        B6.129-Tg(APPSw)40Btla
  • nervous system phenotype
  • amyloid beta deposits (MGI Ref ID J:86629)
    • 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
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:86629)
    • 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

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 (MGI Ref ID J:42613)
    • 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
    • mice have 7- to 8-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes
    • diffuse amyloid beta deposits are detected in the hippocampus and frontal cortex at 24-26 months of age
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:42613)
    • 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
    • mice have 7- to 8-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes
    • diffuse amyloid beta deposits are detected in the hippocampus and frontal cortex at 24-26 months of age

Tg(APPSw)40Btla/Tg(APPSw)40Btla

        D2.129-Tg(APPSw)40Btla
  • nervous system phenotype
  • *normal* nervous system phenotype (MGI Ref ID J:86629)
    • no amyloid beta deposits are observed in 13.5 month-old mice

Gene & Allele Details

Allele Symbol Tg(APPSw)40Btla
Allele Name transgene insertion 40, Bruce Lamb
Common Name(s) APPK670/M671; 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 NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Expressed Gene APP, amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease), human
Promoter APP, amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease), 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
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(APPSw)40Btla

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, transgenic carriers may be bred together, to wildtype siblings, or to C57BL/6J 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.
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
006472   D2.129(B6)-Tg(APPSw)40Btla/J
View Strains carrying   Tg(APPSw)40Btla     (3 strains)

View Strains carrying other alleles of APP     (12 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:

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

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: B6.129-Tg(APPSw)40Btla/J
Stock Number: 005300

Price Details

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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 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.

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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.
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