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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.
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 B6SJLF1/J (RRID:IMSR_JAX:100012) 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.
When maintaining a live colony, hemizygous mice may be bred to B6SJLF1/J (RRID:IMSR_JAX:100012). Males are very aggressive and are housed at lower densities to help reduce fighting as well as given alpha twists for enrichment. Breeders receive shacks and alpha twists to reduce aggression and decrease pre-wean loss.
Colony's Current Health Status Report
Multiple coat colors: Agouti, Albino,Black, Chinchilla, Dilute Brown.
Colony is sized to accommodate orders of up to 50 or more mice within the age range of 4-8 weeks. Larger quantities may be available, please contact the distributing center directly for more details at csmmrrc@jax.org.
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.
Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.
1 The distribution fee covers the expense of rederiving mice from a live mouse; 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.
2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.
3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.
4 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.