Strain Detail Sheet

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

Gene Details [Including genotyping protocols]

(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:

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

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:(provided by MGI)      Extend all MPTs
      assigned by genotype
Tg(APPswe,PSEN1dE9)85Dbo/-
        B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
  • mortality/aging
    • premature death (MGI Ref ID J:160557)
      • about 40% of mice are lost by 12 months of age
  • behavior/neurological phenotype
    • abnormal spatial learning (MGI Ref ID J:160557)
      • severely impaired performance in a morris water maze with much longer latencies to reach a hidden platform
      • performance in a morris water maze declines between 3 and 12 months of age
    • abnormal spatial learning (MGI Ref ID J:172426)
      • 6 month old mutants exhibit slower visuospatial learning than control mice
      • in the visuospatial re-learning test performed at 9, 11, 13, 15, and 18 months of age, mutants exhibit a decrease in the speed of re-learning the task compared to controls
    • impaired passive avoidance behavior (MGI Ref ID J:160557)
  • nervous system phenotype
  • other phenotype
  • taste/olfaction phenotype
    • taste/olfaction phenotype (MGI Ref ID J:172426)
      • mutants do not exhibit Alzheimer's disease-related impairments in olfactory performance in tests based on an operant conditioning procedure and in tests based on a habituation/dishabituation procedure


The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Tg(APPswe,PSEN1dE9)85Dbo/-
        B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
  • nervous system phenotype
    • amyloid beta deposits (MGI Ref ID J:129021)
      • insoluble amyloid beta42 is increased 2-fold in cerebrum of sucrose-fed mice as compared to water-fed control
      • total amyloid beta levels are increased by 3.6 fold in sucrose fed mice
      • amyloid beta deposition is increased by 2.9-fold as determined by immunohistochemical and morphometric analysis in sucrose-fed mice
    • amyloid beta deposits (MGI Ref IDs J:113200, J:113199)
      • sparse deposits observed at 21 weeks of age, however, numerous deposits are observed at 45 and 60 weeks (MGI Ref ID J:113199)
      • deposits are more extensive in females (MGI Ref ID J:113199)
      • level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 20 weeks of age (MGI Ref ID J:113199)
      • senile plaques detected by thioflavin S or the anti-amyloid beta antibody, 3D6, as early as 4 months of age (MGI Ref ID J:113200)
      • plaques are restricted to cortex and hippocampus at time points up to 12 months of age (MGI Ref ID J:113200)
      • plaques increase in number and size over time (MGI Ref ID J:113200)
      • exhibits an overall increase in soluble and insoluble amyloid beta peptide 40 and 42 between 4 and 12 months (MGI Ref ID J:113200)
    • cerebral amyloid angiopathy (MGI Ref ID J:113200)
      • exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
      • amyloid deposition is observed in leptomeningeal vasculature
  • behavior/neurological phenotype
    • abnormal spatial learning (MGI Ref ID J:129021)
      • transgenic mice fed sucrose water failed to learn Morris water maze test after 5 days of training
      • water-fed transgenic mice retained some learning ability over 5 day test period, but did not perform as well in the water maze test as non-transgenic controls
    • increased drinking behavior (MGI Ref ID J:129021)
      • mice fed sucrose water exhibited increased water consumption
  • homeostasis/metabolism phenotype
    • impaired glucose tolerance (MGI Ref ID J:129021)
      • mice fed sucrose water displayed an impaired glucose tolerance as compared to water-fed control
    • increased circulating cholesterol level (MGI Ref ID J:129021)
      • total cholesterol, but not HDL, levels are increased 30% in mice fed sucrose water as compared to water-fed control
    • increased circulating insulin level (MGI Ref ID J:129021)
      • fasting plasma insulin levels are increased 3 fold in mice fed sucrose water as compared to water-fed control
    • increased circulating triglyceride level (MGI Ref ID J:113199)
      • elevated plasma triglyceride levels observed in females at 15 weeks of age
  • cardiovascular system phenotype
    • vasculature congestion (MGI Ref ID J:113200)
  • other phenotype
    • amyloidosis (MGI Ref ID J:129021)
      • amyloid beta deposits (MGI Ref ID J:129021)
        • insoluble amyloid beta42 is increased 2-fold in cerebrum of sucrose-fed mice as compared to water-fed control
        • total amyloid beta levels are increased by 3.6 fold in sucrose fed mice
        • amyloid beta deposition is increased by 2.9-fold as determined by immunohistochemical and morphometric analysis in sucrose-fed mice
      • amyloid beta deposits (MGI Ref IDs J:113200, J:113199)
        • sparse deposits observed at 21 weeks of age, however, numerous deposits are observed at 45 and 60 weeks (MGI Ref ID J:113199)
        • deposits are more extensive in females (MGI Ref ID J:113199)
        • level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 20 weeks of age (MGI Ref ID J:113199)
        • senile plaques detected by thioflavin S or the anti-amyloid beta antibody, 3D6, as early as 4 months of age (MGI Ref ID J:113200)
        • plaques are restricted to cortex and hippocampus at time points up to 12 months of age (MGI Ref ID J:113200)
        • plaques increase in number and size over time (MGI Ref ID J:113200)
        • exhibits an overall increase in soluble and insoluble amyloid beta peptide 40 and 42 between 4 and 12 months (MGI Ref ID J:113200)
      • cerebral amyloid angiopathy (MGI Ref ID J:113200)
        • exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
        • amyloid deposition is observed in leptomeningeal vasculature
  • growth/size phenotype
    • increased body weight (MGI Ref ID J:129021)
      • mice fed sucrose water consistently gained weight over study time period (2 months- 8 months)
      • sucrose-fed mice increased body weight by 17% over water-fed controls
Tg(APPswe,PSEN1dE9)85Dbo/-
        Background Not Specified
  • nervous system phenotype
    • nervous system phenotype (MGI Ref ID J:145530)
      • striatal volume is similar in both transgenic and wild-type at either 6 or 12 months of age
      • abnormal medium spiny neuron morphology (MGI Ref ID J:145530)
        • nuclei of medium spiny stellate neurons in both 6 and 12 month old transgenics are smaller and darker than wild-type
      • decreased neuron number (MGI Ref ID J:145530)
        • numbers of neurons are reduced in striatum of 12, but not 6, month old transgenics
      • neuron degeneration (MGI Ref ID J:145530)
        • numbers of neurons are reduced in striatum of 12, but not 6, month old transgenics
        • reduced neuron density is observed in striatum of 12, but not 6, month old transgenics
Tg(APPswe,PSEN1dE9)85Dbo/-
        involves: C3H/HeJ * C57BL/6J
  • nervous system phenotype
    • amyloid beta deposits (MGI Ref IDs J:139071, J:87691)
      • plaques are abundant in hippocampus and cortex by 9 months of age (MGI Ref ID J:87691)
      • occasional deposits can be found in mice as young as 6 months of age (MGI Ref ID J:87691)
      • ratio of amyloid beta peptide 40:42 is 0.50:1 (MGI Ref ID J:87691)
      • deposits observed in hippocampus by 6 months of age (MGI Ref ID J:139071)
    • reduced long term potentiation (MGI Ref ID J:139071)
      • transient long term potentiation (t-LTP) is reduced in transgenics and is age-independent
  • other phenotype
    • amyloid beta deposits (MGI Ref IDs J:139071, J:87691)
      • plaques are abundant in hippocampus and cortex by 9 months of age (MGI Ref ID J:87691)
      • occasional deposits can be found in mice as young as 6 months of age (MGI Ref ID J:87691)
      • ratio of amyloid beta peptide 40:42 is 0.50:1 (MGI Ref ID J:87691)
      • deposits observed in hippocampus by 6 months of age (MGI Ref ID J:139071)
  • behavior/neurological phenotype
    • abnormal spatial reference memory (MGI Ref ID J:139071)
      • transgenic mice exhibit a 4-5% higher preference for the arm of the radial arm water maze that held the platform on the previous day
      • 13 month old transgenic mice commit more errors in the water maze than controls, at 7 months of age both groups test similarly
    • impaired coordination (MGI Ref ID J:139071)
      • 14 month old transgenic mice exhibit a reduced ability to maintain balance on a rotarod
  • growth/size phenotype
    • decreased body weight (MGI Ref ID J:139071)
      • at 14 months, transgenics weigh less than controls

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

Research Applications

  • Models for Human Disease
  • Neurobiology

Strain Origin

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

Special Considerations

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

Health Status Report

Colony's Current Health Status Report

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

Order Request Information

Availability Level

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.

Conditions of Distribution [Including applicable technology transfer agreements]

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.

Fees

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.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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