B6J.B6N-App^{tm1.1(APP)Mdk}/J

Stock number: 038920
Product name: APP-GR wt

Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Humanized App (amyloid beta precursor protein) wt APP-GR knock-in/knock-out mice carry a ~350 kb fragment of human APP replacing the mouse App locus. This strain may be useful for research involving late onset Alzheimer's disease.

Detailed description

Amyloid beta (A4) precursor protein (APP) is a type I integral membrane protein that is cleaved to form a number of peptides, in particular, the amyloid-β-peptide, a component of the amyloid plaques associated with Alzheimer's disease. These humanized App knock-in/knock-out mice carry a 350 kb fragment of human APP replacing the mouse App locus. Mice homozygous for the mutation are viable and fertile. These mice may be useful for studying APP function and late onset Alzheimer's disease.

Development

The targeting vector was designed to insert a 344 kb (Chr21:25,880,264-26,224,036) fragment of the human APP (apolipoprotein) in place of 268 kb (Chr16:84,750,107-85,019,011) of the mouse App gene on chromosome 16. The construct included a loxP-flanked neomycin selection cassette. In addition, there is also a APP-DT (non-coding antisense RNA) in the human genome segment. The insertion disrupts App transcription. The genomic sequences are from human assembly GRCh38.p14 and the mouse assembly GRCm39. The construct was electroporated into C57BL/6N-PRX-B6N embryonic stem cells (ES). The neomycin cassette was removed by transient expression of Cre. Correctly targeted ES cells were injected into blastocysts. Chimeric animals were backcrossed to C57BL/6J mice for at least 5 generations. Mice were crossed to carry the Tc(HSA17)1Mdk and Psen1^{tm1.1(PSEN1)Mdk} alleles. Upon arrival, mice were bred to C57BL/6J for at least one generation and the Isr(HSA17)1Mdk and Psen1^{tm1.1(PSEN1)Mdk} alleles were bred out of the strain prior to distribution/cryopreservation.

Allele

Symbol: App^{tm1.1(APP)Mdk}
Name: targeted mutation 1.1, Michael D Koob
MGI accession ID: MGI:7565473
Generation method: Targeted
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: APP-GR
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: C57BL/6NTac
Molecular note: The targeting vector is designed to insert a 343 kb (Chr21:25880264 - 26224036) fragment of the human APP (apolipoprotein) in place of 268 kb (Chr16:84750107 - 85019011) of the mouse App gene. The construct includes an FRT-flanked neomycin selection cassette. In addition, there is also a APP-DT (non-coding antisense RNA) in the human genome segment. The insertion disrupts App transcription.The neomycin cassette was removed by transient expression of cre.