Strain Detail Sheet

Strain Name:
B6.Cg-Apptm1Dbo Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
Stock Number:
042050-JAX
Citation ID:
RRID:MMRRC_042050-JAX
Other Names:
APP/PS1xmAPP-/- , Keiko

Strain Information

Gene Details

Apptm1Dbo
Name: amyloid beta precursor protein; targeted mutation 1, David R Borchelt
Synonyms: App-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 16
Alteration at locus: Knockout
App
Name: amyloid beta precursor protein
Synonyms: betaAPP, Abeta, protease nexin II, Adap, Cvap, appican, E030013M08Rik
Type: Gene
Species: Mouse
Chromosome: 16
Alteration at locus: Knockout
NCBI: 11820
VEGA: 16
HGNC: HGNC:620
Homologene: 56379
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PSEN1
Name: presenilin 1 (Alzheimer disease 3)
Type: Gene
Species: Homo sapiens (human)
Chromosome: 14
Alteration at locus: Knockout
APP
Name: amyloid beta precursor protein
Type: Gene
Species: Homo sapiens (human)
Chromosome: 21
Alteration at locus: Knockout
Tg(APPswe,PSEN1dE9)85Dbo
Name: transgene insertion 85, David R Borchelt
Synonyms: APdE9, 2xTg Ad, APPswe/PS1deltaE9, Mo/Hu APPswe PS1dE9, APPswe/PS1dE9, APP/PS1, APP-PS1
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic
Genetic Alterations
Tg(APPswe,PSEN1dE9)85Dbo - The two expression plasmids (Mo/HuAPP695swe and PS1-de9) were designed to each be controlled by independent mouse prion protein (PrP) promoter elements, directing transgene expression predominantly to CNS neurons. The Mo/HuAPP695swe transgene expresses a "humanized" mouse amyloid beta (A4) precursor protein gene modified at three amino acids to reflect the human residues and further modified to contain the K595N/M596L (otherwise known as K670N/M671L) mutations linked to familial Alzheimers. The PS1-dE9) transgene expresses a mutant human presenilin 1 carrying the exon-9-deleted variant (PSEN1dE9) associated with familial Alzheimer's disease. These constructs were coinjected into B6C3HF2 pronuclei and insertion of the transgenes occurred at a single locus.

Apptm1Dbo - A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a region of the App gene encoding the promoter and exon 1. The construct was electroporated into 129S7/SvEvBrd-derived AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice.
Genotype Determination
ES Cell Line
AB2.1 (129S7/SvEvBrd-Hprtb-m2)

Strain Description

Phenotype

Homozygous: The B6.129S7-App(tm1Dbo)/J Jackson Labs stock number 004133 does not express any mouse APP gene.

Hemizygous: The B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/J carry one human mutated APP and PS1 gene. Homozygous is lethal.

Mammalian Phenotype Terms
Allelic Composition: (Genetic Background: )
MeSH Terms
  • Adaptation, Ocular/genetics
  • Adaptation, Ocular/physiology
  • Alzheimer Disease/genetics
  • Alzheimer Disease/pathology
  • Amyloid beta-Peptides/metabolism
  • Amyloid beta-Protein Precursor/genetics
  • Amyloid beta-Protein Precursor/metabolism
  • Amyloid beta-Protein Precursor/pharmacology
  • Animals
  • Astrocytes/metabolism
  • Cell Proliferation/genetics
  • Cells, Cultured
  • Cytokines/metabolism
  • Disease Models, Animal
  • Exploratory Behavior/physiology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia/metabolism
  • Morpholinos/pharmacology
  • Mutation/genetics
  • Phenotype
  • Presenilin-1/genetics
  • Presenilin-1/metabolism
  • Amyloid beta-Protein Precursor/deficiency
  • Gliosis/genetics
  • Locomotion/genetics
  • Mice, Mutant Strains
  • Brain/metabolism
  • Gene Transfer Techniques
  • Genes
  • Genetic Vectors
  • Immunoblotting
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Mice/genetics
  • Mice, Transgenic/genetics
  • Polymerase Chain Reaction
  • Presenilin-1
  • Transgenes
Strain Development
Heterozygous B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/J (JAX Strain #005864) were bred with Homozygous B6.129S7-App tm1Dbo/J (JAX Strain #004133). All offspring were genotyped to confirm phenotype.
Suggested Control Mice
Wild-type littermates

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.

Research Applications

  • Immunology and Inflammation
  • Models for Human Disease
  • Neurobiology

Strain Origin

Donor
Colin Combs, Ph.D., University of North Dakota.
David Borchelt, Ph.D., University of Florida.
Primary Reference

Manocha GD, Floden AM, Rausch K, Kulas JA, McGregor BA, Rojanathammanee L,Puig KR, Puig KL, Karki S, Nichols MR, Darland DC, Porter JE, Combs CK. APPRegulates Microglial Phenotype in a Mouse Model of Alzheimer's Disease. JNeurosci. 2016 Aug 10;36(32):8471-86. doi: 10.1523/JNEUROSCI.4654-15.2016. (Medline PMID: 27511018)

Zheng H, Jiang M, Trumbauer ME, Sirinathsinghji DJ, Hopkins R, Smith DW,Heavens RP, Dawson GR, Boyce S, Conner MW, Stevens KA, Slunt HH, Sisoda SS, Chen HY, Van der Ploeg LH. beta-Amyloid precursor protein-deficient mice show reactivegliosis and decreased locomotor activity. Cell. 1995 May 19;81(4):525-31. (Medline PMID: 7758106)

Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Borchelt DR.Co-expression of multiple transgenes in mouse CNS: a comparison of strategies.Biomol Eng. 2001 Jun;17(6):157-65. (Medline PMID: 11337275)

Colony and Husbandry Information

Health Status Report

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.

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email csmmrrc@jax.org.

Appearance

Coat Color
Black
Eye
Unknown

Breeding

MMRRC Breeding System
Sib-mating
Breeding Scheme(s)
Sib-Mating
  • 2 females and 1 male per cage are bred for 6-8 months.
Generation
F2
Overall Breeding Performance
Good

Reproductive Statistics

NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: 6 to 8 months 6 to 8 months
Average litter size
4-6
Recommended wean age
3-4 weeks
Average Pups Weaned
4-6

Order Request Information

Availability Level

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.

Conditions of Distribution

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.

Fees

- Products for this strain are Not Yet Available for Ordering
- If you register interest in this strain, you will be notified when it becomes available for ordering.
To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.