Strain Name    : B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax

Stock Number : 034832-JAX

Other Names   : This strain was formerly available as JAX Mice stock number 5864. Mo/Hu APPswe PS1dE9, APPswe/PS1dE9 line 85 congenics, APPswe/PS1dE9, APP/PS1

Gene Information

(provided by MGI)
Transgene: Tg(APPswe,PSEN1dE9)85Dbo
Name: transgene insertion 85, David R Borchelt
Alteration at locus: Transgenic
Genetic Alterations:

Genotype Determination:

ES Cell Line: Not applicable

Phenotype

Homozygous phenotype: Not evaluated
Hemizygous phenotype: Double transgenic mice express a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9) both directed to CNS neurons. Both mutations are associated with early-onset Alzheimer's disease. The "humanized" Mo/HuAPP695swe transgene allows the mice to secrete a human A-beta peptide. Both the transgenic peptide and holoprotein can be detected by antibodies specific for human sequence within this region (Signet Laboratories' monoclonal 6E10 antibody). The included Swedish mutations (K595N/M596L) elevate the amount of A-beta produced from the transgene by favoring processing through the beta-secretase pathway. This "humanized" Mo/HuAPP695swe protein is immunodetected in whole brain protein homogenates. The transgenic mutant human presenilin protein (PS1-dE9), which in high levels displaces detectable endogenous mouse protein, is also immunodetected in whole brain protein homogenates. The donating investigator reports that transgenic mice develop beta-amyloid deposits in brain by six to seven months of age. These animals also display a slight alteration in their tail phenotype that is believed to be due to the mixed genetic background of the strain and is not related to transgene expression. Hemizygous mice on the C57BL/6 background (N9B6) exhibit a high incidence of seizures, as detected by video-EEG. 25% of transgenic mice, 3 to 3.5 months in age, exhibit at least 1 seizure. By 4.5 months of age, seizure incidence increases to 55%. 10-15% mortality is reported for transgenic mice on the congenic (N9) C57BL/6 background (Minkeviciene et al. J Neurosci. 2009). Hemizygous mice, on the congenic C57BL/6J background (N13), 17-18 weeks in age, exhibit epileptiform discharges as detected by video-EEG. Mortality was 38% (6/16) and some mutant mice experienced spontaneous seizures during the experiments. Antiepileptic drugs (carbamazepine, phenytoin, valproate) reduce the frequency of spontaneous electrographic epileptiform discharges (Ziyatdinova et al. Epilepsy Res 2011). These mice may be useful in studies of neurological disorders of the brain, specifically Alzheimer's disease, amyloid plaque formation, and aging.

Mammalian Phenotype Terms:
Allelic Composition: Tg(APPswe,PSEN1dE9)85Dbo/0 (Genetic Background: B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax )

Allelic Composition: Tg(APPswe,PSEN1dE9)85Dbo/0 (Genetic Background: B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax )

Allelic Composition: Tg(APPswe,PSEN1dE9)85Dbo/0 (Genetic Background: involves: C3H * C57BL/6 )

Allelic Composition: Tg(APPswe,PSEN1dE9)85Dbo/0 (Genetic Background: involves: C3H/HeJ * C57BL/6J )

Strain of Origin: C3B6

Strain genetic background: B6.Cg

Strain Development: 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 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 occured at a single locus. Founder line 85 was obtained and the resulting colony was maintained as a hemizygote by crossing transgenic mice to B6C3F1/J mice. Transgenic mice were then backcrossed to C57BL/6J for at least 8 generations.

Suggested Control Mice: Wild-ype littermates

  • Models for Human Disease
  • Neurobiology

Donor: David Borchelt, Ph.D., McKnight Brain Institute, University of Florida

Primary Reference:

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

When maintaining a live colony, hemizygotes may be bred with wildtype siblings.

Colony's Current Health Status Report

For more information about this colony's health status contact csmmrrc@jax.org

Order Request Information

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.

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.
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.
Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description
Distribution
Fee/unit (US $)
Units Notes
034832-JAX-HEMI-FHemizygous female
034832-JAX-HEMI-MHemizygous male
034832-JAX-WT-FWild type female
034832-JAX-WT-MWild type male
$218.00
Non-Profit
Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).

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.

2 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.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

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 above). 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.



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.