Strain Detail Sheet

Strain Name    :

C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax

Stock Number :

034843-JAX

Other Names   :

This strain was formerly available as JaxMice stock number 7027. Tg-SwDI/B, APPSwDI

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Transgene: Tg(Thy1-APPSwDutIowa)BWevn
Name: transgene insertion B, William E Van Nostrand
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 phenotype: Homozygote phenotype is expected to be similar to hemizygote phenotype.
Hemizygous phenotype: These transgenic mice express neuronally derived human amyloid beta-precursor protein, APP gene, 770 isoform, containing the Swedish K670N/M671L, Dutch E693Q and Iowa D694N mutations, under the control of the mouse thymus cell antigen 1, theta, Thy1, promoter. Mice hemizygous for the transgenic insert exhibit expression of human amyloid beta precursor protein in the cortex, hippocampus and brain stem with lower expression detected in the cerebellum. At age three months hemizygotes show a progressive accumulation of insoluble amyloid beta 40 and 42 peptides in brain tissue. The levels of accumulation of amyloid beta peptides is 12 to 14 fold higher in brain microvessels than in whole forebrain tissue homogenates. Fibrillar microvascular accumulations of amyloid beta peptides begin at approximately six months of age. Diffuse plaque-like deposits of amyloid beta that are similar to the plaques observed in human patients with the Dutch and Iowa familial disorders are initially detected at approximately 3 months of age in the subiculum, hippocampus and cortex. After six months of age the diffuse plaque-like deposits increase in number and spread to the olfactory bulb and thalamic region. Amyloid beta deposits are detected throughout the forebrain by 12 months of age. The donating investigator has made the strain homozygous and reports that mice homozygous for the transgenic insert are viable and fertile. This mutant mouse strain may be useful in studies of Alzheimer's disease and cerebral amyloid angiopathy.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Tg(Thy1-APPSwDutIowa)BWevn/-
        involves: C57BL/6
  • nervous system phenotype
    • abnormal astrocyte morphology (MGI Ref ID J:124911)
      • astrocyte numbers and density are enhanced in thalamic and cortical regions where fibrillar amyloid beta deposits are prominent
    • abnormal microglial cell physiology (MGI Ref ID J:124911)
      • activation of microglial and astrocytes is elevated in cortex
      • microglial cells show significantly increased levels of complement proteins C1q, C3 and C4
    • amyloid beta deposits (MGI Ref ID J:89848)
      • over the course of 1 year, progressive and robust accumulation of insoluble amyloid beta-40 and -42 peptides is observed in mouse brains; increase in peptides is first observed at 3 months and increases markedly by 12 months
      • soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels
      • amyloid beta deposits are observed in the regions of the subiculum, hippocampus, and cortex at ~3 months; by ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months
      • parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature
    • amyloid beta deposits (MGI Ref ID J:124911)
      • deposits are largely in parenchyma and in diffuse form in cortex
    • cerebral amyloid angiopathy (MGI Ref IDs J:124911, J:89848)
      • levels of amyloid beta-40 and -42 peptides are 12- and 14-fold higher in forebrain microvessels than in whole forebrain homogenates at 12 months of age; at ~3 months, levels in vasculature of forebrains is higher than whole forebrain tissue (MGI Ref ID J:89848)
      • vascular amyloid beta accumulation is prominent in the thalamus and subiculum, and increases with age such that 45-55% of vessels are affected at 12 months of age; at ~6 months of age, amyloid beta d eposits in and around microvessels in the thalamus and subiculum are observed (MGI Ref ID J:89848)
      • microvascular amyloid beta accumulations are mainly fibrillar (MGI Ref ID J:89848)
      • some arterioles in these brain regions show strong vascular and perivascular amyloid beta depostion, while blood vessel-rich regions like the hippocampal fissure show large accumulations of perivascular amyloid beta (MGI Ref ID J:89848)
      • evidence of microhemorrhage is observed in microvessels with amyloid beta deposits (MGI Ref ID J:89848)
      • microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions (MGI Ref ID J:124911)
  • immune system phenotype
    • abnormal microglial cell physiology (MGI Ref ID J:124911)
      • activation of microglial and astrocytes is elevated in cortex
      • microglial cells show significantly increased levels of complement proteins C1q, C3 and C4
  • other phenotype
    • amyloidosis (MGI Ref ID J:89848)
      • mutants show decreased clearance of the mutant form of amyloid beta peptides compared to wild-type amyloid beta
      • amyloid beta deposits (MGI Ref ID J:124911)
        • deposits are largely in parenchyma and in diffuse form in cortex
      • amyloid beta deposits (MGI Ref ID J:89848)
        • over the course of 1 year, progressive and robust accumulation of insoluble amyloid beta-40 and -42 peptides is observed in mouse brains; increase in peptides is first observed at 3 months and increases markedly by 12 months
        • soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels
        • amyloid beta deposits are observed in the regions of the subiculum, hippocampus, and cortex at ~3 months; by ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months
        • parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits ha ving a more compact structure suggesting a fibrillar nature
      • cerebral amyloid angiopathy (MGI Ref IDs J:124911, J:89848)
        • levels of amyloid beta-40 and -42 peptides are 12- and 14-fold higher in forebrain microvessels than in whole forebrain homogenates at 12 months of age; at ~3 months, levels in vasculature of forebrains is higher than whole forebrain tissue (MGI Ref ID J:89848)
        • vascular amyloid beta accumulation is prominent in the thalamus and subiculum, and increases with age such that 45-55% of vessels are affected at 12 months of age; at ~6 months of age, amyloid beta deposits in and around microvessels in the thalamus and subiculum are observed (MGI Ref ID J:89848)
        • microvascular amyloid beta accumulations are mainly fibrillar (MGI Ref ID J:89848)
        • some arterioles in these brain regions show strong vascular and perivascular amyloid beta depostion, while blood vessel-rich regions like the hippocampal fissure show large accumulations of perivascular amyloid beta (MGI Ref ID J:89848)
        • evidence of microhemorrhage is observed in microvessels with amyloid beta deposits (MGI Ref ID J:89848)
        • microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions (MGI Ref ID J:124911)
  • cardiovascular system phenotype
    • abnormal blood circulation (MGI Ref ID J:119251)
      • reduced cerebral blood flow, CBF, response (21% increase) to whisker stimulation is observed relative to controls (38% increase) at 9 months
      • with myocardin gene transfer, CBF response drops to 10% in transgenic mice, a decrease of 50%, while it increased to 27% with shSRF gene transfer compared to 19% in shGFP controls

Strain of Origin: C57BL/6

Strain genetic background: C57BL/6

Strain Development: A transgenic construct containing 2.1kb of the human amyloid beta-precursor protein, APP gene, 770 isoform, with the Swedish K670N/M671L, Dutch E693Q and Iowa D694N mutations, under the control of the mouse thymus cell antigen 1, theta, Thy1, promoter was injected into fertilized C57BL/6 mouse eggs. Founder line B was subsequently established and homozygotes generated.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be C57BL/6N. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Suggested Control Mice: Wild-ype littermates

Research Applications

  • Models for Human Disease
  • Neurobiology

Strain Origin

Donor: William Van Nostrand, Ph.D., Stony Brook University

Primary Reference:

Davis J; Xu F; Deane R; Romanov G; Previti ML; Zeigler K; Zlokovic BV; Van Nostrand WE, Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor., J Biol Chem 2004 May 7;279(19):20296-306 (Medline PMID: 14985348)

Colony and Husbandry Information

Special Considerations

When maintaining a live colony, these mice may be bred as homozygotes.

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
034843-JAX-HOM-FHomozygous female
034843-JAX-HOM-MHomozygous 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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