Tg(APPSw)40Btla
Transgene Detail

Summary

• Symbol: Tg(APPSw)40Btla
• Name: transgene insertion 40, Bruce Lamb
• MGI ID: MGI:3510594
• Synonyms: APP^K670/M671, APP^K670N/M671L, R1.40, R1.40-YAC, Tg(APP*Swe)40Btla
• Transgene: Tg(APPSw)40Btla Location: unknown Genetic Position: Chr13, Syntenic
• Alliance: Tg(APPSw)40Btla page

Transgene origin

• Germline Transmission: Earliest citation of germline transmission: J:42613
• Parent Cell Line: R1 (ES Cell)
• Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺

Transgene description

• Transgene Type: Transgenic (Humanized sequence, Inserted expressed sequence)
• Mutation: Insertion
• Tg(APPSw)40Btla expresses 1 gene
  Transgene expresses:
  

  Organism

  Expressed Gene

  Homolog in Mouse

  Note

  human

  APP (351)

  App	(MGI:88059)

  The gene encodes the Swiss mutation.

• Mutation details: 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. (J:42613, J:58050, J:73622)

Disease models

Find Mice (IMSR)

• Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
• Carrying this Mutation: Mouse Strains: 4 strains available Cell Lines: 0 lines available

References

• Original: J:42613 Lamb BT, et al., Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice. Hum Mol Genet. 1997 Sep;6(9):1535-41
• All: 20 reference(s)