STOCK App^tm1Sud/J

Stock number: 008390
Research areas: Neurobiology Research

Description

These targeted mutant (knock-in line ADF) mice carry an insertion incorporating a truncated exon 16 of the mouse amyloid beta (A4) precursor protein (App) gene as well as the Swedish mutant exon 16 and London/Dutch mutations of exon 17. Truncated exon 16 is incorporated into the sAPPbeta-FLAG transcript, but exon 17 is not expressed. No overt phenotype has been observed. Homozygotes are viable and fertile. This strain may be useful in studies of Alzheimer's disease.

Detailed description

These targeted mutant (knock-in line ADF) mice carry an insertion incorporating a truncated exon 16 of the mouse amyloid beta (A4) precursor protein (App) gene as well as the Swedish mutant exon 16 and London/Dutch mutations of exon 17. Truncated exon 16 is incorporated into the sAPPbeta-FLAG transcript, but exon 17 is not expressed. No overt phenotype has been observed. Homozygotes are viable and fertile. This strain may be useful in studies of Alzheimer's disease.

Development

The first portion of the targeting vector incorporates a wildtype mouse App exon 16 (truncated after residue KM) followed by a FLAG tag (2 repeats), a stop codon, a poly A signal region from the human growth hormone gene, and a pair of neomycin resistance cassettes which are flanked by a pair of FRT sites. All of these elements are flanked by a single pair or loxP sites. This construct is followed by an additional copy of exon 16 carrying the Swedish mutation and modified version of exon 17 carrying the London mutation plus the Dutch mutation.

This vector was introduced to (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. Resultant mice were crossed with an FLP strain (unspecified background) to remove the neomycin cassettes. Truncated exon 16 is incorporated into the sAPPbeta-FLAG transcript, but exon 17 is not expressed. This line (commonly called ADF) has been crossed with C57BL/6 and maintained on a mixed background by the donating laboratory.

Allele

Symbol: App^tm1Sud
Name: targeted mutation 1, Thomas C Sudhof
MGI accession ID: MGI:3783884
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence
Marker symbol: App
Marker name: amyloid beta (A4) precursor protein
Chromosome: 16
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: The targeting vector incorporates a wildtype mouse App exon 16 (truncated after residue KM) followed by a FLAG tag (2 repeats), a stop codon, a poly A signal region from the human growth hormone gene, and a pair of neomycin resistance cassettes which are flanked by a pair of FRT sites. All of these elements are flanked by a single pair or loxP sites. This construct is followed by an additional copy of exon 16 carrying the Swedish mutation and modified version of exon 17 carrying the London mutation plus the Dutch mutation. Mice were crossed with an FLP strain (unspecified background) to remove the neomycin cassettes. Truncated exon 16 is incorporated into the sAPPbeta-FLAG transcript, but exon 17 is not expressed.