B6.Cg-Apoe^{tm1.1(APOE*4)Adiuj} App^tm1.1Dnli/MsasnJ

Stock number: 039775
Product name: APOE4/APP^SAA
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

The APOE4/APP^SAA 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 E693G (Arctic) and T714I (Austrian) mutations in the mouse App (amyloid beta (A4) precursor protein) gene. Mice also carry a humanized ApoE knock-in mutation (sequence coding for isoform E4). This strain may be useful for studying Alzheimer's disease.

Detailed description

The APOE4/APP^SAA 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 E693G (Arctic) and T714I (Austrian) mutations in the mouse App (amyloid beta (A4) precursor protein) gene. Mice also carry a humanized ApoE knock-in mutation (sequence coding for isoform E4). This strain may be useful for studying Alzheimer's disease.

Double homozygous mice are viable and fertile.

Development

This double mutant APOE4/APP^SAA mouse line was generated by crossing 2 single mutant lines. Specifically, hAbeta^SAA mice (Stock No. 034711) harboring the humanizing Aβ region R684H, F681Y, and G676R mutations, and the KM670/671NL (Swedish) mutation, as well as the E693G (Arctic; GAA to GGA) and T714I (Austrian; ACC to ATA) mutations in the mouse App (amyloid beta (A4) precursor protein) gene were crossed to APOE4 KI mice (Stock No. 027894) carrying a humanized ApoE knock-in mutation (sequence coding for isoform E4). Resulting APOE4/APP^SAA mice were backcrossed to C57BL/6J (Stock No. 000664) for at least 2 generations. 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.

Allele

Symbol: App^tm1.1Dnli
Name: targeted mutation 1, Denali Therapeutics
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.

Allele

Symbol: Apoe^{tm1.1(APOE*4)Adiuj}
Name: targeted mutation 1.1, MODEL-AD Center
MGI accession ID: MGI:5810209
Generation method: Targeted
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: APOE^epsilon4
Marker symbol: Apoe
Marker name: apolipoprotein E
Marker synonyms: AD2; APO-E; ApoE4; APOEA; LDLCQ5; LPG
Chromosome: 7
Strain of origin: C57BL/6J
Expressed genes: APOE,apolipoprotein E,human
Site of expression: Endogenous mouse elements direct human APOE gene sequence (including exons 2, 3 and 4 and some 3' UTR sequence).
Molecular note: The targeting vector contains a 3' FRT flanked neo cassette and 1.5 kb of human APOE gene sequence including exons 2, 3, 4 and a portion of the 3'UTR sequence (the APOE4 isoform) which is used to replace exons 2, 3 and most of exon 4 of the endogenous sequence. The human APOE sequence carries a 2 nucleotide A-to-T substitution in intron 3. Flp-mediated recombination removed the FRT-flanked neo cassette.