Strain Detail Sheet

Strain Name    :

B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2JMmjax

Stock Number :

034836-JAX

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Transgene: Tg(PDGFB-APPSwInd)20Lms
Name: transgene insertion 20, Lennart Mucke
Alteration at locus: Transgenic

Genetic Alterations:

Genotype Determination:

ES Cell Line: Not Applicable

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

Phenotype

Homozygous: Not evaluated
Hemizygous: These transgenic mice express a mutant form of the human amyloid protein precursor bearing both the Swedish (K670N/M671L) and the Indiana (V717F) mutations (APPSwInd). Expression of the transgenic insert is directed by the human platelet-derived growth factor beta polypeptide (PDGFB) promoter. Hemizygotes express immunodetectable transgene product in cerebral neurons, with the highest level of expression occurring in the neocortex and hippocampus. Enzyme-linked immunosorbent assay (ELISA) analysis reveals approximate total amyloid beta peptides and 42 amino acid length amyloid beta peptides in neocortical and hippocampal tissue from mutant mice. At five to seven months of age diffuse amyloid beta peptides deposition in the dendate gyrus and neocortex forms. Amyloid deposition is progressive with all transgenic mice exhibiting plaques by age eight to 10 months. Video-EEG monitoring of 4 to 7 month old hemizygous transgenic mice, N10+ on the C57BL/6J background, reveals hippocampal hyperexcitability and cortical and hippocampal spontaneous nonconvulsive seizures. The mice are immobile, with no myoclonic behavior observed, during the non-convulsive electroencephalographic seizures. Pentylenetetrazole induced seizures have earlier onset, are more severe and result in more frequent deaths (50% develop fatal status epilepticus) than wildtype controls (Palop et al. Neuron 2007). This mutant mouse strain represents a model that may be useful in studies of the pathogenesis of Familial Alzheimer's Disease and possible therapeutic treatments. Pups born of carrier females have shown an increased mortality rate in our colonies.  The Donating Researcher has observed an approximately 15% mortality rate in the first 6 months of life.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Tg(PDGFB-APPSwInd)20Lms/-
        B6.Cg-Tg(PDGFB-APPSwInd)20Lms
  • nervous system phenotype
    • abnormal cerebral cortex pyramidal cell morphology (MGI Ref ID J:118589)
      • at 6 months and 12 to 16 months of age, 30% fewer pyramidal cells in the entorhinal cortex express Reelin than in wild-type mice
      • however, no neuron loss is observed
Tg(PDGFB-APPSwInd)20Lms/-
        B6.D2-Tg(PDGFB-APPSwInd)20Lms
  • nervous system phenotype
    • abnormal neuron morphology (MGI Ref ID J:100954)
      • dystrophic neurites are associated with plaques
    • amyloid beta deposits (MGI Ref ID J:100954)
      • mice develop amyloid peptide deposits by 5-7 months of age
  • other phenotype
    • amyloid beta deposits (MGI Ref ID J:100954)
      • mice develop amyloid peptide deposits by 5-7 months of age


The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Tg(PDGFB-APPSwInd)20Lms/-
        involves: C57BL/6 * DBA/2
  • mortality/aging
    • premature death (MGI Ref IDs J:121330, J:141084, J:87150)
      • (MGI Ref ID J:141084)
      • mice show premature death of unclear etiology with >15% mortality exhibited by 6 months, compared to all ot her genotypes (MGI Ref ID J:121330)
      • high rate of premature (6 months or earlier) death (MGI Ref ID J:87150)
  • behavior/neurological phenotype
    • abnormal long term object recognition memory (MGI Ref ID J:121330)
      • at 4-7 months of age, mice transgenic mice with wild-type Mapt expression take longer to locate the platform in the cued version of the Morris water maze test compared to transgenic mice heterozygous or homozygous for Mapt deletion
    • abnormal spatial learning (MGI Ref IDs J:121330, J:141084)
      • in the hidden platform version of the Morris water maze, non-trangenic controls, regardless of Mapt genotype learn the task over 3 days, whereas transgenic mice with wild-type expression of Mapt show no evidence of learning (MGI Ref ID J:121330)
      • in probe trials where the platform is removed, mice show no learning, displaying no significantly elevated crossings of the target quadrant after 5 days of training (MGI Ref ID J:121330)
      • in a Morris water maze, mice fail to favor the target platform location unlike wild-type mice (MGI Ref ID J:141084)
    • decreased anxiety-related response (MGI Ref ID J:141084)
      • mice exhibit disinhibition-like behaviors in an elevated plus maze compared with wild-type mice
    • hyperactivity (MGI Ref IDs J:121330, J:141084)
      • (MGI Ref ID J:141084)
      • mice show hyperactivity in the Y-maze, a new cage, and elevated-plus maze compared to other transgenic mice or non-transgenic controls; this persists in mice 12-16 months of age (MGI Ref ID J:121330)
    • increased susceptibility to pharmacologically induced seizures (MGI Ref ID J:121330)
      • mice are abnormally sensitive to pentylenetetrazole (PTZ)-induced seizures with 20% suffering fatal status epilepticus at a PTZ dose not lethal in non-transgenic controls
  • nervous system phenotype
    • abnormal neuron morphology (MGI Ref ID J:121330)
      • mice show neuritic dystrophy around amyloid plaques
      • abnormal neuron differentiation (MGI Ref ID J:121330)
        • aberrant sprouting of hippocampal axons is observed in transgenic mice
    • amyloid beta deposits (MGI Ref IDs J:121330, J:62290, J:87150)
      • diffuse immunoreactive amyloid deposits detected in dentate gyrus and neocortex of mice aged 5 to 7 months old (MGI Ref ID J:62290)
      • all mice exhibit plaques by age 8 to 10 months (MGI Ref ID J:62290)
      • at 4-7 months and 14-18 months, Abeta plaque deposition is observed, at levels the same as other transgenics heterozygous null for Mapt (MGI Ref ID J:121330)
      • soluble and insoluble Abeta-40 and -42 peptide deposits at 6-10 months (MGI Ref ID J:87150)
    • increased susceptibility to pharmacologically induced seizures (MGI Ref ID J:121330)
      • mice are abnormally sensitive to pentylenetetrazole (PTZ)-induced seizures with 20% suffering fatal status epilepticus at a PTZ dose not lethal in non-transgenic controls
    • neurodegeneration (MGI Ref ID J:62290)
      • neurodegeneration is indicated by an age dependent decrease in density of synaptophysin-immunoreactive presynaptic terminals
  • other phenotype
    • amyloid beta deposits (MGI Ref IDs J:121330, J:62290, J:87150)
      • diffuse immunoreactive amyloid deposits detected in dentate gyrus and neocortex of mice aged 5 to 7 months old (MGI Ref ID J:62290)
      • all mice exhibit plaques by age 8 to 10 months (MGI Ref ID J:62290)
      • at 4-7 months and 14-18 months, Abeta plaque deposition is observed, at levels the same as other transgenics heterozygous null for Mapt (MGI Ref ID J:121330)
      • soluble and insoluble Abeta-40 and -42 peptide deposits at 6-10 months (MGI Ref ID J:87150)

Strain of Origin: (C57BL/6J X DBA/2) F2

Strain genetic background: B6.Cg

Strain Development: A transgenic construct containing the mutant human amyloid protein precursor APPSwInd under the control of human platelet-derived growth factor beta polypeptide, simian sarcoma viral (v-sis) oncogene homolog, (PDGFB) promoter, was injected into C57BL/6 X DBA/2 F2 one-cell embryos. Heterozygous founder animals were bred to C57BL/6 X DBA/2 F1 mice. The resulting transgenic mice were then backcrossed for 12 generations on the C57BL/6J background.

Suggested Control Mice: Wild-ype littermates

Research Applications

  • Models for Human Disease
  • Neurobiology

Strain Origin

Donor: Lennart Mucke , Ph.D., Gladstone Institute of Neurological Disease

Primary Reference:

Mucke L; Masliah E; Yu GQ; Mallory M; Rockenstein EM; Tatsuno G; Hu K; Kholodenko D; Johnson-Wood K; McConlogue L, High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation., J Neurosci 2000 Jun 1;20(11):4050-8 (Medline PMID: 10818140)

Colony and Husbandry Information

Special Considerations

When maintaining a live colony, hemizygous males are bred to wildtype siblings or to C57BL/6J inbred females. Pups born of carrier females have shown an increased mortality rate in our colonies. The Donating Researcher has observed an approximately 15% mortality rate in the first 6 months of life.

This strain was formerly available as JaxMice stock number 6293. PDGF-hAPP695,751,770V171F, KM670/671NL, hAPPJ20

Health Status Report

Colony's Current Health Status Report

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

Appearance

Coat color:

Other:

Breeding

MMRRC Breeding System:

Breeding Scheme(s):

    Generation:

    Overall Breeding Performance:

    Reproductive Statistics

    Viability and Fertility: Unknown

    Average litter size:

    Recommended wean age:

    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]

    MTA Required for MMRRC:034836

    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
    034836-JAX-HEMI-FHemizygous female
    034836-JAX-HEMI-MHemizygous male
    034836-JAX-WT-FWild type female
    034836-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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