Strain Detail Sheet

Strain Name    :

B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/Mmjax

Stock Number :

034842-JAX

Other Names   :

This strain was formerly available as JaxMice stock number 7002. BRI-Abeta42A line 12e

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Transgene: Tg(Prnp-ITM2B/APP695*42)A12Emcg
Name: transgene insertion A12, Eileen McGowan
Alteration at locus: Transgenic
Promoter: Prnp
Name: prion protein
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: Mice hemizygous for this BRI-Abeta42 transgene are viable and fertile with a normal lifespan and no obvious behavioral abnormalities. Transgenic BRI-Abeta42 mRNA is expressed in a pattern characteristic of the mouse prion protein promoter; highest transgene expression levels are detected in the cerebellar granule cells and hippocampus, followed by the cortex, pons, thalamus, and midbrain. Wildtype BRI protein is cleaved by furin or a furin-like protease near the COOH-terminus which releases a soluble 23 amino acid peptide. In the transgenic fusion protein, Abeta1-42 is fused to the C terminus of the BRI protein at the furin-like cleavage site such that cleavage results in efficient Abeta1-42 secretion into the lumen or extracellular space. Therefore, these mice specifically express the Abeta1-42 isoform in the absence of human amyloid beta protein precursor (APP) overexpression. In contrast to BRI-Abeta40 transgenic mice, hemizygous BRI-Abeta42 mice accumulate detergent-insoluble amyloid-beta with age and develop cored plaques in the cerebellum at as early as three months of age. Development of forebrain pathology occurs later, and is more variable. Extracellular Abeta plaques are not present consistently in the hippocampus and entorhinal/piriform cortices until 12 months of age. BRI-Abeta42 mice also develop extensive congophillic amyloid angiopathy with age. These mutant mice may be useful in neurological studies of Alzheimer's disease, neurodegeneration, and amyloid plaque formation.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Tg(Prnp-ITM2B/APP695*42)A12Emcg/-
        involves: C3H * C57BL/6
  • nervous system phenotype
    • abnormal forebrain morphology (MGI Ref ID J:101023)
      • forebrain pathology only consistently develops after 12 months of age
    • amyloid beta deposits (MGI Ref ID J:101023)
      • cored plaques can be observed as early as 3 months in molecular layer of cerebella of transgenic mice and becoming more pronounced with age; occasional extracellular plaques are seen in the entorhinal/piriform cortices and hippocampus at 6 months of age, but aren't consistently found until >12 months of age
      • oldest mice show widespread pathology with cored and diffuse plaques in cerebellum, cortex, hippocampus, and olfactory bulb
      • extracellular amyloid plaques show dense amyloid cores with radiating fibrils; many bundles of dystrophic neurites are observed at the periphery of these plaques
      • compact plaques range from 38 um in diameter at 3 months to 58 um at 1-18 months
      • tau pathology is not evident
      • endogenous mouse Abeta is detected in some cored plaques and in diffuse deposits in older mice
    • gliosis (MGI Ref ID J:101023)
      • reactive gliosis is associated with plaques
  • other phenotype
    • amyloidosis (MGI Ref ID J:101023)
      • Abeta1-42 peptide levels in 3-month old transgenic brains are ~1- to 1.5-fold higher than levels in 3- and 6-month oldTg(APPSWE)2576Kahs controls
      • amyloid beta deposits (MGI Ref ID J:101023)
        • cored plaques can be observed as early as 3 months in molecular layer of cerebella of transgenic mice and becoming more pronounced with age; occasional extracellular plaques are seen in the entorhinal/piriform cortices and hippocampus at 6 months of age, but aren't consistently found until >12 months of age
        • oldest mice show widespread pathology with cored and diffuse plaques in cerebellum, cortex, hippocampus, and olfactory bulb
        • extracellular amyloid plaques show dense amyloid cores with radiating fibrils; many bundles of dystrophic neurites are observed at the periphery of these plaques
        • compact plaques range from 38 um in diameter at 3 months to 58 um at 1-18 months
        • tau pathology is not evident
        • endogenous mouse Abeta is detected in some cored plaques and in diffuse deposits in older mice

Strain of Origin: C3B6F1

Strain genetic background: B6;C3

Strain Development: The BRI-Abeta42 transgene was generated with a mouse prion promoter upstream of a BRI-Abeta42 fusion construct. This fusion construct contained a cDNA sequence from human type 2 transmembrane protein (BRI or ITM2B) fused in-frame with a "wildtype APP695" cDNA sequence encoding amyloid-beta42 (Abeta42) at the furin-like cleavage site; the C-terminal 23 amino acid ABri peptide of BRI was replaced with the Abeta42 sequence. The transgene was injected into the pronuclei of single-cell embryos from C3B6F1 × B6 mice and then implanted into pseudopregnant females. Mice from the founder with the highest Abeta42 plasma levels, line BRI-Abeta42A (12e), were maintained on a mixed B6C3 background prior to arrival at The Repository.

Suggested Control Mice: Wild-ype littermates

Research Applications

  • Models for Human Disease
  • Neurobiology

Strain Origin

Donor: Eileen McGowan, Ph.D., Mayo Clinic College of Medicine

Primary Reference:

McGowan E; Pickford F; Kim J; Onstead L; Eriksen J; Yu C; Skipper L; Murphy MP; Beard J; Das P; Jansen K; Delucia M; Lin WL; Dolios G; Wang R; Eckman CB; Dickson DW; Hutton M; Hardy J; Golde T, Abeta42 is essential for parenchymal and vascular amyloid deposition in mice., Neuron 2005 Jul 21;47(2):191-9 (Medline PMID: 16039562)

Colony and Husbandry Information

Special Considerations

When maintaining a live colony, hemizygous mice can be bred with wildtype littermates or with B6C3F1/J.

Health Status Report

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.

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.

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
034842-JAX-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.

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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