Mouse Strain Datasheet
Mouse Strain Datasheet
These 5XFAD transgenic mice overexpress mutant human APP(695) with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) Familial Alzheimer's Disease (FAD) mutations along with human 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.
Robert Vassar, Northwestern University
| Genetic Background | Generation |
|---|---|
|
100012 B6SJLF1/J |
N11+N25
|
| Allele Type |
|---|
| Transgenic (Inserted expressed sequence, Humanized sequence) |
These 5XFAD transgenic mice overexpress both mutant human APP(695) with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) Familial Alzheimer's Disease (FAD) mutations and human 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 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 the mixed C57BL/6 and SJL background (see MMRRC stock 34840), intraneuronal Abeta-42 accumulation is observed starting at 1.5 months of age, just prior to amyloid deposition and gliosis, which begins at two months of age. On a congenic C57BL/6J genetic background (see MMRRC stock 34848) it has been the observation of the MMRRC that this phenotype is not as robust as that demonstrated in the mixed C57BL/6 and SJL background (view data). In addition, these mice have reduced synaptic marker protein levels, increased p25 levels, neuron loss, and memory impairment in the Y-maze test. 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/wildtype 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 (rs108080490 and rs107649577; 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 B6SJL F1 at every generation, SJL content is segregating in the progeny of these animals. Mice produced from this cross could be genotypically heterozygous, homozygous or wildtype for this locus. This variant may be of particular interest to those studying the role played by TREM2 in Alzheimer's Disease pathology.
NOTE: This 5XFAD transgene is also available on a C57BL/6J background (see MMRRC stock 34848), which does not carry the Trem2S148E allele.
A transgene was designed with a mutant human amyloid beta (A4) precursor protein (APP) cDNA sequence (altered to include the APP K670N/M671L (Swedish) + I716V (Florida) + V717I (London) Familial Alzheimer's Disease (FAD) mutations) inserted into exon 2 of the mouse Thy1 gene. A second transgene was designed with a mutant human presenilin 1 (Alzheimer disease 3) (PSEN1 or PS1) cDNA sequence (altered to include the PS1 M146L + L286V FAD mutations) inserted into exon 2 of the mouse Thy1 gene. Both transgenes were added together in equal proportions and co-injected into the pronuclei of single-cell "C57/B6XSJL" hybrid embryos. Founders from the highest APP expressing line (Tg6799) were bred with (B6/SJL)F1 for more than 10 generations with stable germ-line transmission and expression of both transgenes, demonstrating that these "5XFAD"; mice breed as single transgenics. Of note, the APP transgene includes the 5' untranslated region and thus contains a putative interleukin-1beta translational enhancer element.
| Expressed Gene | PSEN1, presenilin 1, human |
|---|---|
| Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera |
| Site of Expression |
| Allele Name | transgene insertion 6799, Robert Vassar |
|---|---|
| Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
| Allele Synonym(s) | Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas; transgene insertion 6799, Robert Vassar |
| Gene Symbol and Name | Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas, transgene insertion 6799, Robert Vassar |
| Gene Synonym(s) | 5XFAD line Tg6799; 5XFAD; Tg6799 |
| Promoter | Thy1, thymus cell antigen 1, theta, mouse, laboratory |
| Expressed Gene | PSEN1, presenilin 1, human |
| Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera |
| Strain of Origin | (C57BL/6 x SJL)F1 |
| Chromosome | 3 |
| General Note | Three transgenic lines coexpressing the APP and PSEN1 proteins at high, medium and low levels, respectively designated Tg6799, Tg7031, and Tg7092, were propagated for analysis, most of which employed Tg6799.
Phenotypic Similarity to Human Syndrome: Macular Degeneration, Age-Related J:214858. |
| Molecular Note | Four familial Alzheimer disease- (FAD-) associated mutations were introduced into a single human amyloid precursor protein cDNA: the "Swedish" double mutation (K670N/M671L); the "Florida" mutation (I716V); and the "London" mutation (V717I). Two FAD-associated mutations, M146L and L286V, likewise were introduced into a human presenilin 1 cDNA. Each cDNA was then cloned independently into the mouse thymus cell antigen 1 gene, replacing a segment that contains thymus-specific elements so that expression of the transgenes is targeted only to the brain. Equal molar amounts of the two transgenes were coinjected into pronuclei of single-celled embryos. |
| Mutations Made By | Robert Vassar, Northwestern University |
When maintaining a live colony, hemizygous mice may be bred to B6SJLF1/J (Stock No. 100012).
When using the 5XFAD mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34840 in your Materials and Methods section.
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