Name: transgene insertion 6799, Robert Vassar
Alteration at locus: Transgenic
ES Cell Line:
Homozygote phenotype is expected to be similar to hemizygote phenotype.
Hemizygous mice are viable and fertile. 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 and rapidly accumulate massive cerebral levels. On the B6SJL F1 genetic background (this strain), 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 (MMRRC:034848) it has been the observation of the MMRRC that this phenotype is not as robust as that demonstrated in the B6SJL hybrid 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 rapidly recapitulate major features of Alzheimer's Disease amyloid pathology and may be useful models of intraneuronal Abeta-42 induced neurodegeneration and amyloid plaque formation.
This strain is segregating heterozygous/wildtype for the retinal degeneration allele Pde6brd1.
Strain of Origin: C57/B6XSJL
Strain genetic background: B6SJL
Strain Development: 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.
Suggested Control Mice: Wild-ype littermates
Donor: Robert Vassar, Ph.D., Northwestern University
Oakley H; Cole SL; Logan S; Maus E; Shao P; Craft J; Guillozet-Bongaarts A; Ohno M; Disterhoft J; Van Eldik L; Berry R; Vassar R, Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation., J Neurosci 2006 Oct 4;26(40):10129-40 (Medline PMID: 17021169)
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1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
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