B6.Cg-App^tm1.1Dnli/J

Stock number: 034711
Product name: hAbeta^SAA, APP-SAA KI
Strain synonyms: hAbeta^Swe,Arc,Aus
Research areas: Neurobiology Research

Description

The hAbeta^SAA (APP-SAA KI) knock-in mouse model of Alzheimer's disease carries humanizing Aβ region R684H, F681Y, and G676R mutations, and the KM670/671NL (Swedish) mutation in exon 16 as well as the E693G (Arctic) and T714I (Austrian) mutations in exon 17 of the mouse App (amyloid beta (A4) precursor protein) gene. Mice recapitulate amyloid plaque pathology in vivo without disturbing intrinsic gene expression.

Detailed description

The hAbeta^SAA (APP-SAA KI) knock-in mouse model of Alzheimer's disease (AD) carries humanizing Aβ region R684H, F681Y, and G676R mutations, and the KM670/671NL (Swedish) mutation in exon 16 as well as the E693G (Arctic) and T714I (Austrian) mutations in exon 17 of the mouse App (amyloid beta (A4) precursor protein) gene. Mice recapitulate amyloid plaque pathology in vivo without disturbing intrinsic gene expression.

As a control, we recommend the hAbeta model (Stock No. 033013), which has the same humanized Abeta region but lacks the three familial AD mutations.

Also see: Alzforum (February 6, 2021).

Development

A targeting vector was used to introduce a series of mutations to the mouse App gene via homologous recombination in B6.Cg-Thy1^a-derived Bruce 4 embryonic stem (ES) cells. R684H (CGC to CAC), F681Y (TTT to TAT), G676R (GGA to AGA) and KM670/671NL (Swedish - AAGATG to AATCTA) mutations were introduced to exon 16, an FRT-flanked PGK-neomycin cassette (in reverse transcriptional orientation) and an F3-flanked PGK-hygromycin cassette (in reverse transcriptional orientation) were place in intron 16, and E693G (Arctic - GAA to GGA) and T714I (Austrian - ACC to ATA) mutations were introduced to exon 17. Resultant mice were crossed with mice expressing FlpE recombinase (OzFlp; Gt(ROSA)26Sor^{tm1.1(UBC-flpe)Ozg}) to remove the PGK-neomycin and PGK-hygromycin cassettes, leaving the modified exons 16 and 17. Subsequent matings were done with C57BL/6J mice by the donating laboratory (see SNP note below).

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: App^tm1.1Dnli
Name: targeted mutation 1, Pascal Sanchez
MGI accession ID: MGI:6437481
Generation method: Targeted
Attributes: Humanized sequence
Synonyms: App^SAA
Marker symbol: App
Marker name: amyloid beta (A4) precursor protein
Marker synonyms: AAA; Abeta; ABPP; AD1; Adap; alpha-sAPP; APPI; appican; betaAPP; CTFgamma; Cvap; E030013M08Rik; PN2; PN-II; preA4; protease nexin II
Chromosome: 16
Strain of origin: B6.Cg-Thy1^a
Molecular note: The targeting vector was used to introduce the human R684H, F681Y, G676R and KM670/671NL (Swedish) mutations into to exon 16. An FRT-flanked PGK-neomycin cassette (in reverse transcriptional orientation), and an F3-flanked PGK-hygromycin cassette (in reverse transcriptional orientation) is placed in intron 16, and the E693G (Artic) and T714I (Austrian) mutations are introduced to exon 17. Flpe-mediated recombination removed the FRT-flanked neomycin and hygromycin cassettes.