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| These BRI-Abeta42 transgenic mice harbor a mouse prion promoter-driven BRI-Abeta42 fusion construct (containing a human type 2 transmembrane protein (BRI or ITM2B) fused in-frame with a "wild-type 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)). As Abeta1-42 is fused to the C terminus of the BRI protein at the furin-like cleavage site, cleavage releases Abeta into the lumen or extracellular space, resulting in efficient secretion of Abeta1-42. Therefore, these BRI-Abeta42 transgenic mice specifically express the Abeta1-42 isoform in the absence of human amyloid beta protein precursor (APP) overexpression and may be useful in neurological studies of Alzheimer's disease, neurodegeneration, and amyloid plaque formation. | |||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Noncarrier x Hemizygote (Female x Male) 14-APR-08 Species laboratory mouse Generation ?+N1F1 (24-DEC-08) Donating Investigator Eileen McGowan, Mayo Clinic College of Medicine 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 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.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.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Tg(Prnp-ITM2B/APP695*42)A12Emcg allele
007182 B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J View Strains carrying Tg(Prnp-ITM2B/APP695*42)A12Emcg (1 strain)
007180 B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J
Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
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
This mouse can be used to support research in many areas including:
APP695 relatedMouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
strains expressing mutant APP
Neurodegeneration
Research Tools
Neurobiology Research
Neurobiology Research
Alzheimer's Disease
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Prnp-ITM2B/APP695*42)A12Emcg | ||
|---|---|---|---|
| Allele Name | transgene insertion A12, Eileen McGowan | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | BRI-Abeta1-42; BRI-Abeta42A; BRI-Abeta42A line 12e; 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 | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera | ||
| Expressed Gene | ITM2B, integral membrane protein 2B, human | ||
| 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] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Prnp-ITM2B/APP695*42)A12Emcg MCA, Melt Curve Analysis
Tg(Prnp-ITM2B/APP695*42)A12Emcg, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
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]
Additional References
Tg(Prnp-ITM2B/APP695*42)A12Emcg relatedStokin GB; Almenar-Queralt A; Gunawardena S; Rodrigues EM; Falzone T; Kim J; Lillo C; Mount SL; Roberts EA; McGowan E; Williams DS; Goldstein LS. 2008. Amyloid precursor protein-induced axonopathies are independent of amyloid-beta peptides. Hum Mol Genet 17(22):3474-86. [PubMed: 18694898] [MGI Ref ID J:140396]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice can be bred with wildtype littermates or with B6C3F1/J (Stock No. 100010). Mating System Noncarrier x Hemizygote (Female x Male) 14-APR-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $243.50 Female or Male Hemizygous for Tg(Prnp-ITM2B/APP695*42)A12Emcg
Pairs /Price (US dollars $) Pair Genotype $297.85 Hemizygous for Tg(Prnp-ITM2B/APP695*42)A12Emcg x Noncarrier $297.85 Noncarrier x Hemizygous for Tg(Prnp-ITM2B/APP695*42)A12Emcg
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Hemizygous for Tg(Prnp-ITM2B/APP695*42)A12Emcg
Pairs /Price (US dollars $) Pair Genotype $387.30 Hemizygous for Tg(Prnp-ITM2B/APP695*42)A12Emcg x Noncarrier $387.30 Noncarrier x Hemizygous for Tg(Prnp-ITM2B/APP695*42)A12Emcg
Additional Supply Details
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Supply Details
| Standard Supply | Repository-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 approximately 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 two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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