B6.Cg-Tg(APPSwe,tauP301L)1Lfa Psen1^tm1Mpm/J

Stock number: 008880
Product name: 3xTg-AD on C57BL/6J
Strain synonyms: 3xTg-AD
Research areas: Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

Stock No. 008880 was never distributed from The Jackson Laboratory and has been discontinued. We are currently developing a C57BL/6J-congenic 3xTg-AD mouse line - see Stock No. 033930.
Researchers may also consider using 3xTg-AD mice on B6;129 genetic background (Stock No. 004807 B6;129-Tg(APPSwe,tauP301L)1Lfa Psen1^tm1Mpm/Mmjax) or the 3xTg-AD mice on 129S4 genetic background (Stock No. 031988 129S4.Cg-Tg(APPSwe,tauP301L)1Lfa Psen1^tm1Mpm/LfaJ).

3xTg-AD mice harbor a Psen1 PS1M146V mutation and the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa)). These mice may be useful for studying plaque and tangle pathology associated with synaptic dysfunction and Alzheimer's disease.

Allele

Symbol: Tg(APPSwe,tauP301L)1Lfa
Name: transgene insertion 1, Frank M LaFerla
MGI accession ID: MGI:2672831
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(APPSwe,tauP301L)1Lfa
Marker name: transgene insertion 1, Frank M LaFerla
Chromosome: 2
Strain of origin: Not Specified
Expressed genes: MAPT,microtubule associated protein tau,human; APP,amyloid beta precursor protein,human
Molecular note: To develop a model of Alzheimer's Disease, mice harboring mutant human APP (Swedish double mutation; K670N, M671L) and MAPT (P301L) as well as Psen^tm1Mpm were generated by microinjection of the APP and MAPT transgenic constructs into single cell embryos harvested from mice homozygous for Psen1^tm1Mpm. Southern blot analysis indicated that both transgenic constructs integrated into the same site. Western blot analysis showed APP and MAPT levels to be ~4 fold higher in hemizygous mice and ~6 (APP) to ~7 (Mapt) fold higher homozygous mice, relative to non transgenic mice. Amyloid-Beta peptide (both 40 and 42) was detected in transgenic mice, with greater levels in homozygous mice than in hemizygous mice. Expression was confined to the CNS. Highest steady state levels of proteins were detected in Alzheimer's Disease related regions including the hippocampus and cerebral cortex. Transgenic protein was not detected in the cerebellum. The transgene inserted on Chr 2 causing a 3 bp deletion.

Allele

Symbol: Psen1^tm1Mpm
Name: targeted mutation 1, Mark P Mattson
MGI accession ID: MGI:1930937
Generation method: Targeted
Marker symbol: Psen1
Marker name: presenilin 1
Chromosome: 12
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Point mutations were introduced into the coding region of exon 5 that altered the codons corresponding to amino acids 145 and 146 from isoleucine and methionine to valine and valine, respectively, and a BstEII restriction site. A lox-P flanked neomycin cassette was also introduced into exon 4. F2 mice exhibited the expected polymorphism of the targeted allele when genomic DNA was amplified with exon 5 specific primers and the products were digested with the appropriate restriction enzyme. Northern blot analysis of total brain RNA using a Psen1 specific antibody showed that the targeted allele was expressed at normal physiological levels in homozygous mutant mice.