B6.129S6(FVB)-App^tm1.1Wevn/Mmjax

Stock number: 030810
Product name: AβPP/KPI^R13I
Strain synonyms: APP/KPI R13I/Mmjax
Research areas: Neurobiology Research

Description

The AβPP/KPI^R13I knockin mice carry an amino acid substitution in the Kunitz proteinase inhibitor (KPI) domain. When subjected to experimentally induced carotid artery thrombosis, mice exhibit a decrease in time to vessel occlusion as compared to wild-type mice. This strain may be useful for studying the regulation of cerebral thrombosis.

Detailed description

App (amyloid beta (A4) precursor protein) is a type I integral membrane protein that is cleaved to form a number of peptides, in particular, the amyloid-β-peptides associated with Alzheimer's disease. The AβPP/KPI^R13I knockin allele substitutes an arginine for isoleucine in the Kunitz proteinase inhibitor (KPI) domain. Isoforms of APP that contain the KPI domain function to inhibit cerebral thrombosis. AβPP/KPI^R13I mice are viable and fertile and express similar levels of APP protein in the brain as wild-type mice. Mice subjected to experimentally induced carotid artery thrombosis exhibit a decrease in time to vessel occlusion as compared to wild-type mice. Following the induction of intracerebral hemorrhage, mice develop smaller hematomas than wild-type mice and APP null mice. This strain may be useful for studying the regulation of cerebral thrombosis.

Development

The targeting vector was designed to substitute an arginine for isoleucine at amino acid position 13 by introducing two point mutations into the arginine codon (CGC to ATC). A loxP-flanked Neomycin cassette also was included in the construct. The R13I mutation is located on a 10 kb long arm fragment 300 bp downstream of exon 7. The construct was electroporated into 129S6/SvEvTac-derived iTL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J to remove the neo cassette. Offspring were backcrossed to C57BL/6NTac for 10 generations. Upon arrival, mice were bred to C57BL/6NJ for at least 1 generation to establish the colony.

Allele

Symbol: App^tm1.1Wevn
Name: targeted mutation 1.1, William Van Nostrand
MGI accession ID: MGI:5903308
Generation method: Targeted
Attributes: Not Applicable
Synonyms: AbetaPP/KPI^R13I
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: 129S6/SvEvTac
Molecular note: The targeting vector was designed to substitute an arginine for isoleucine at amino acid position 13 by introducing two point mutations into the arginine codon (CGC to ATC). A loxP-flanked Neomycin cassette also was included in the construct. The R13I mutation is located on a 10 kb long arm fragment 300 bp downstream of exon 7. Cre-mediated recombination removed the loxP-flanked neo. Expression of APP protein is not affected.