B6.Cg-App^em8Msasn/J

Stock number: 039774
Product name: APP^SFL
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

The APP^SFL knock-in mouse model of Alzheimer's disease carries humanizing Aβ region R684H, F681Y, and G676R mutations, and the KM670/671NL (Swedish) mutation, as well as the I716V (Florida) and V717I (London) mutations in the mouse App (amyloid beta (A4) precursor protein) gene and is associated with familial Alzheimer's disease.

Detailed description

The APP^SFL knock-in mouse model of Alzheimer's disease carries humanizing Aβ region R684H, F681Y, and G676R mutations, and the KM670/671NL (Swedish) mutation, as well as the I716V (Florida) and V717I (London) mutations in the mouse App (amyloid beta (A4) precursor protein) gene and is associated with familial Alzheimer's disease.

Heterozygous and homozygous mice are viable and fertile.

Development

The APP^SFL knock-in mouse model of Alzheimer's disease carries humanizing Aβ region R684H, F681Y, and G676R mutations, and the KM670/671NL (Swedish) mutation, as well as the I716V (Florida) and V717I (London) mutations in the mouse App (amyloid beta (A4) precursor protein) gene.

Plasmids encoding single guide RNAs designed to introduce Florida I716V (isoleucine to valine) and London V717I (valine to isoleucine) mutations in the App gene and the cas9 nuclease were introduced into the cytoplasm of fertilized eggs with well recognized pronuclei from hAbeta^Swe mice. hAbeta^Swe mice already carry humanizing Aβ region R684H, F681Y, and G676R mutations, and the KM670/671NL (Swedish) mutations associated with familial Alzheimer's disease. The mice also harbor a humanized APOE*4 mutation (see Stock No. 027894) and a Trem2*R47H KI mutation (see Stock No. 027918).

Surviving embryos were transferred to pseudopregnant females. Progeny were screened by DNA sequencing to identify correctly targeted pups, which were then bred to C57BL/6J mice (Stock No. 000664) for germ line transmission. This APP^SFL colony was backcrossed to hAbeta mice (Stock No. 033013) for three generations. The APOE*4, Trem2*R47H KI, and hAbeta mutations were bred out of the colony. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Important note about App isoforms and exon numbering:The App-201 isoform (695 aa protein) is encoded by 16 exons, of which the Abeta sequence is encoded by exon 14. The App-206 isoform (770 aa protein) is encoded by 18 exons, of which the Abeta sequence is encoded by exon 16.

Allele

Symbol: App^em8Msasn
Name: endonuclease-mediated mutation 7, Michael Sasner
MGI accession ID: MGI:7703878
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Synonyms: APP^SFL
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: Not Specified
Molecular note: Using CRISPR/Cas9 technology, the humanizing A(beta) region R684H, F681Y, and G676R mutations, and the KM670/671NL (Swedish) mutation, as well as the I716V (Florida) and V717I (London) mutations were introduced in the mouse App (amyloid beta (A4) precursor protein) gene.