Mutations: APP KM670/671NL (Swedish), APP V717I (London), APP E693Q (Dutch)
Modification: APP: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl<+>; C57BL/6 and maintained on a mixed background
Availability: The Jackson Lab: Stock# 008390; Cryopreserved
These knock-in mice, commonly called ADF, carry an insertion incorporating parts of exon 16 and exon 17 of APP. Homozygotes are viable and fertile. No overt phenotype has been observed.
The targeting vector incorporates a wild-type 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 of loxP sites. This construct is followed by an additional copy of exon 16 carrying the Swedish mutation and a modified exon 17 with the London and Dutch mutations. Progeny were crossed with an FLP strain to remove the neomycin cassettes. The truncated exon 16 is incorporated into an sAPPβ-FLAG transcript, but exon 17 is not expressed.
No Available Further Reading