These 5XFAD transgenic mice overexpress both mutant human amyloid beta (A4) precursor protein 695 (APP) with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) Familial Alzheimer's Disease (FAD) mutations and human presenilin 1 (PS1) harboring two FAD mutations, M146L and L286V. Expression of both transgenes is regulated by neural-specific elements of the mouse Thy1 promoter to drive overexpression in the brain. Mice from this 6799 founder line have high APP expression correlating with high burden and accelerated accumulation of the 42 amino acid species of beta-amyloid (Abeta-42). 5XFAD mice generate Abeta-42 almost exclusively, rapidly accumulating massive cerebral levels. On this mixed C57BL/6 and SJL background (MMRRC stock 34840), intraneuronal Abeta-42 accumulation is observed starting at 1.5 months of age in hemizygotes, just prior to amyloid deposition and gliosis, which begins at two months of age. On a congenic C57BL/6J genetic background (<a href="http://www.mmrrc.org/catalog/getSDS.php?mmrrc_id=34848">see MMRRC stock 34848</a>) it has been the observation of the MMRRC that this phenotype in hemizygotes is not as robust as that demonstrated in hemizygotes from the mixed C57BL/6 and SJL background (<a href="https://www.mmrrc.org/icc/strains/repository/34848/34848%2034840%20data.pdf&amp;access=public">view data</a>). In addition, these mice have reduced synaptic marker protein levels, increased p25 (formally Cdk5) levels, neuron loss, reduced anxiety, poor novel object recognition, impaired conditioned behavior and memory impairment in the Y-maze test. 5XFAD males exhibit increased home cage aggression and decreased social investigation in both males and females. 5XFAD transgenic mice recapitulate major features of Alzheimer's Disease amyloid pathology and may be useful models of intraneuronal Abeta-42 induced neurodegeneration and amyloid plaque formation. Hemizygous mice are viable and fertile. This strain is segregating heterozygous/wild-type for the retinal degeneration allele Pde6brd1. It should be noted that the SJL genetic background contains the Trem2S148E allele - a naturally occurring variant at position 48351151-48351152 on Chr 17 (<a href="http://useast.ensembl.org/Mus_musculus/Variation/Sample?db=core;r=17:48351102-48351202;v=rs108080490;vdb=variation;vf=14473644">rs108080490</a> and <a href="http://useast.ensembl.org/Mus_musculus/Variation/Sample?db=core;r=17:48350652-48351652;v=rs107649577;vdb=variation;vf=14110567">rs107649577</a>; Ensembl GRCm38.p6). This TC to GA transition results in a serine to glutamic acid substitution at amino acid 148 (S148E). Because this model (MMRRC stock 34840) is maintained by backcrossing transgenic animals to a B6SJLF1 hybrid at every generation, SJL content is segregating in the progeny of these animals. Mice produced from this cross could be genotypically heterozygous, homozygous or wild-type for this Trem2S148E. This variant may be of particular interest to those studying the role played by TREM2 (triggering receptor expressed on myeloid cells 2) in Alzheimer's Disease pathology. NOTE: This 5XFAD transgene is also available on a C57BL/6J background (<a href="http://www.mmrrc.org/catalog/getSDS.php?mmrrc_id=34848">see MMRRC stock 34848</a>), which does not carry the Trem2S148E allele.

These 5XFAD transgenic mice overexpress mutant human amyloid beta (A4) precursor protein 695 (APP) with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) Familial Alzheimer's Disease (FAD) mutations along with human presenilin 1 (PS1) harboring two FAD mutations, M146L and L286V. Both transgenes are regulated by the mouse Thy1 promoter to drive overexpression in the brain. 5XFAD mice recapitulate major features of Alzheimer's Disease amyloid pathology and may be a useful model of intraneuronal Abeta-42 induced neurodegeneration and amyloid plaque formation.

This strain is hosted by NIH's MMRRC, which partners with JAX for the distribution of this and other strains. The MMRRC site maintains this strain where you can make a purchase.