B6.129S7-App^tm1Dbo/J

Stock number: 004133
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Homozygous App mice weigh 15%-20% less than age-matched wild-type controls, and exhibit decreased locomotor activity and forelimb grip strength. Reactive gliosis is seen in some homozygous mice at 14 weeks of age. This beta-amyloid precursor protein (APP) knock-out strain offers a model useful in studies related to Alzheimer's disease.

Detailed description

At birth, mice homozygous for the targeted allele are viable, and do not display any gross physical or behavioral abnormalities. No App gene product (mRNA or protein) is detected. Body weight is 15-20% less than that observed in wildtype age-matched control mice. By 14 weeks of age the mice exhibit evidence of reactive gliosis. Neurological evaluation reveals significantly reduced forelimb grip strength and decreased locomotor activity. This mutant strain offers a model useful in studies related to Alzheimer's disease.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a region of the App gene encoding the promoter and exon 1. The construct was electroporated into 129S7/SvEvBrd-derived AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice.

Allele

Symbol: App^tm1Dbo
Name: targeted mutation 1, David R Borchelt
MGI accession ID: MGI:2136847
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: App-
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: 129S7/SvEvBrd-Hprt1^b-m2
Molecular note: A neomycin resistance cassette replaced a 3.8 kb sequence including the promoter region and first exon. Northern blot analysis did not detect mRNA in brain or kidney of homozygous mutant mice.