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PrP.APPsi transgenic mice express human APP (amyloid beta precursor protein) bearing the Swedish and Indiana mutations. In addition, a second transgene carrying a human KRT14 (K14) promoter driving skin-specific expression of EGFP has been co-integrated with the APP transgene. Hemizygous mice develop Alzheimer's disease (AD) pathology at 11-14 months of age.
These PrP.APPsi transgenic mice express a chimeric mouse/human amyloid precursor protein (APP695) bearing the Swedish (KM570/571NL) and Indiana (V617F) mutations associated with Alzheimer's disease (APP695swe/ind) under the control of a brain specific mouse prion promoter (Prnp or PrP). To facilitate genotyping, the PrP.APPsi transgene was co-integrated with a human KRT14 (K14) promoter driving skin-specific expression of EGFP. EGFP can be visualized with goggles. Mice hemizygous for the PrP.APPsi transgene are viable and fertile. Hemizygotes develop Alzheimer's disease pathology in the cortex and hippocampus as well as vascular deposits in the meninges of the cerebellum and cortex beginning at 11-14 months of age. Aβ deposits are of a mixed pathology in which diffuse deposits are more abundant than cored-neuritic deposits.
The mouse amyloid beta (A4) precursor protein (App) sequence was first modified to contain a humanized amyloid-beta (Abeta) domain. This mouse/human chimeric APP (called mo/huAPP695 or APP695) was further mutated to incorporate the Swedish (KM570/571NL) and Indiana (V617F) mutations associated with Alzheimer's disease. This APP695Swe/Ind sequence was placed downstream of the brain-specific mouse prion promoter (Prnp). The transgene was co-integrated with a transgene in which the human KRT14 (K14) promoter drives skin-specific expression of EGFP into the pronucleus of fertilized eggs from (C3H/HeJ x C57BL/6J) F1 matings. Transgene positive founders (line 3) were maintained on the mixed background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize B6C3F1/J oocytes (JAXStock No. 100010).
Moore BD, Levites Y, Xu G, Hampton H, Adamo MF, Croft CL, Futch HS, Moran C, Fromholt S, Janus C, Prokop S, Dickson D, Lewis J, Giasson BI, Golde TE, Borchelt DR. Soluble brain homogenates from diverse human and mouse sources preferentially seed diffuse Aβ plaque pathology when injected into newborn mouse hosts. Free Neuropathol. 2022 Jan 11;3(9):3-9. doi: 10.17879/freeneuropathology-2022-3766. Epub 2022 Mar 23. (Medline PMID: 35494163)
Xu G, Fromholt S, Borchelt DR. Modeling the Competition between Misfolded Aβ Conformers That Produce Distinct Types of Amyloid Pathology in Alzheimer's Disease. Biomolecules. 2022 Jun 24;12(7):886. doi: 10.3390/biom12070886. (Medline PMID: 35883442)
Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-reports.
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.
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.
The donor or their institution limits the distribution to non-profit institutions only.