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Strain Name:

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

Stock Number:

007002

Availability:

Repository- Live

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Genes & Alleles   APP695;   ITM2B;   Prnp;   Tg(Prnp-ITM2B/APP695*42)A12Emcg;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Transgenic
Mating SystemNoncarrier x Hemizygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Eileen McGowan,   Mayo Clinic College of Medicine
Generation?+N0 (28-DEC-07)

Strain Description
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 (Stock No. 006880), hemizygous BRI-Abeta42 mice accumulate detergent-insoluble amyloid-beta with age and develop cored plaques in the cerebellum at as early as 3 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.

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 Jackson Laboratory.

Related Disease (OMIM) Terms

Alzheimer Disease; AD
Mammalian Phenotype Terms assigned by genotype

Tg(Prnp-ITM2B/APP695*42)A12Emcg/0

        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

Gene & Allele Details

Allele Symbol Tg(Prnp-ITM2B/APP695*42)A12Emcg
Allele Name transgene insertion A12, Eileen McGowan
Common Name(s) BRI-Abeta1-42; BRI-Abeta42A; RI-Abeta42A (12e);
Mutation Made By Eileen McGowan,   Mayo Clinic College of Medicine
Strain of Origin(C3H x C57BL/6)F1 X C57BL/6
Expressed Gene ITM2B, integral membrane protein 2B, human
Expressed Gene APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera
Promoter Prnp, prion protein, mouse, laboratory
Molecular Note The transgene was generated with a mouse prion promoter upstream of a BRI-Abeta42 fusion construct, containing 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. Mice from the founder with the highest Abeta42 plasma levels, line BRI-Abeta42A (12e) were donated to the Jackson Laboratory. Transgenic fusion protein expression approximates levels of endogenous mouse APP expression and is expressed in patterns characteristic of the Prnp promoter, with highest expression in cerebellar granule cells and hippocampus. Full length Abeta fusion protein is most highly expressed with processed Abeta42 peptide expressed at lower levels [MGI Ref ID J:101023] [MGI Ref ID J:120781]

Control Information

  Control
   Noncarrier (approximate)
 
  Considerations for Choosing Controls

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygous mice can be bred with wildtype littermates or with B6C3F1/J (Stock No. 100010).
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying other alleles of APP695     (8 strains)

Strains carrying other alleles of ITM2B
007180   B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J
006880   B6;C3-Tg(Prnp-ITM2B/APP695*40)1Emcg/J
View Strains carrying other alleles of ITM2B     (2 strains)

View Strains carrying other alleles of Prnp     (18 strains)

Additional Web Information

Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Animal Health Reports

Room Number           AX11

Research Applications

This mouse can be used to support research in many areas including:

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Alzheimer's Disease (strains expressing mutant APP)
Alzheimer's Disease
Neurodegeneration

Research Tools
Neurobiology Research

APP695 related

Neurobiology Research
Alzheimer's Disease

References

Selected Reference(s)

Kim J; Onstead L; Randle S; Price R; Smithson L; Zwizinski C; Dickson DW; Golde T; McGowan E. 2007. Abeta40 inhibits amyloid deposition in vivo. J Neurosci 27(3):627-33. [PubMed: 17234594]  [MGI Ref ID J:117413]

Lewis PA; Piper S; Baker M; Onstead L; Murphy MP; Hardy J; Wang R; McGowan E; Golde TE. 2001. Expression of BRI-amyloid beta peptide fusion proteins: a novel method for specific high-level expression of amyloid beta peptides. Biochim Biophys Acta 1537(1):58-62. [PubMed: 11476963]  [MGI Ref ID J:120781]

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. 2005. Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47(2):191-9. [PubMed: 16039562]  [MGI Ref ID J:101023]

Price and Supply Information

Strain Name: B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J
Stock Number: 007002

Price Details

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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