| 
| ||||||||||||||||||
| 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 "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)). 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
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N5F1pN1
Generation DefinitionsDonating 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; with highest expression in the cerebellar granule cells and hippocampus, followed by the cortex, pons, thalamus, and midbrain. The BRI-Abeta42 fusion protein takes advantage of the BRI protein that is normally cleaved by furin or a furin-like protease near the COOH-terminus (releasing a soluble 23 amino acid peptide in the wild-type BRI protein). 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 mice specifically express the Abeta1-42 isoform in the absence of human amyloid beta protein precursor (APP) overexpression. In contrast to the BRI-Abeta40 strain (Stock No. 006880), hemizygous BRI-Abeta42 mice accumulate detergent-insoluble amyloid-beta with age and develop cored plaques as ear;y as three months in the cerebellum. Development of forebrain pathology occurs later and is more variable. Extracellular Abeta plaques are not consistently present in the hippocampus and entorhinal/piriform cortices until 12 months. 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.This is a C57BL/6J backcross of Stock No. 007002. In an attempt to offer alleles on well-characterized or multiple gene tic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
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 "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. The transgene was injected into the pronuclei of single-cell embryos from C3B6F1 x 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 (as Stock No. 007002). Upon arrival, some mice were backcrossed to C57BL/6J for at least five generations to generate this congenic strain (Stock No. 007182).
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (108 strains)
007002 B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/Mmjax
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
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Alzheimer Disease; AD
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Cerebral Amyloid Angiopathy, Itm2b-Related, 1 (ITM2B)
Cerebral Amyloid Angiopathy, Itm2b-Related, 2 (ITM2B)
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Prnp-ITM2B/APP695*42)A12Emcg/0
involves: C3H * C57BL/6
- nervous system phenotype
- abnormal forebrain morphology
- forebrain pathology only consistently develops after 12 months of age (MGI Ref ID J:101023)
- amyloid beta deposits
- 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 (MGI Ref ID J:101023)
- oldest mice show widespread pathology with cored and diffuse plaques in cerebellum, cortex, hippocampus, and olfactory bulb (MGI Ref ID J:101023)
- extracellular amyloid plaques show dense amyloid cores with radiating fibrils; many bundles of dystrophic neurites are observed at the periphery of these plaques (MGI Ref ID J:101023)
- compact plaques range from 38 um in diameter at 3 months to 58 um at 1-18 months (MGI Ref ID J:101023)
- tau pathology is not evident (MGI Ref ID J:101023)
- endogenous mouse Abeta is detected in some cored plaques and in diffuse deposits in older mice (MGI Ref ID J:101023)
- gliosis
- reactive gliosis is associated with plaques (MGI Ref ID J:101023)
- other phenotype
- amyloidosis
- 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 (MGI Ref ID J:101023)
- amyloid beta deposits
- 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 (MGI Ref ID J:101023)
- oldest mice show widespread pathology with cored and diffuse plaques in cerebellum, cortex, hippocampus, and olfactory bulb (MGI Ref ID J:101023)
- extracellular amyloid plaques show dense amyloid cores with radiating fibrils; many bundles of dystrophic neurites are observed at the periphery of these plaques (MGI Ref ID J:101023)
- compact plaques range from 38 um in diameter at 3 months to 58 um at 1-18 months (MGI Ref ID J:101023)
- tau pathology is not evident (MGI Ref ID J:101023)
- endogenous mouse Abeta is detected in some cored plaques and in diffuse deposits in older mice (MGI Ref ID J:101023)
This mouse can be used to support research in many areas including:
Neurobiology Research
Alzheimer's Disease
Neurodegeneration
Research Tools
Neurobiology Research
Genes & Alleles
Gene & Allele Information provided by MGI
| 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 | 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] | ||
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 provided by MGI
Selected Reference(s)
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 relatedKim 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]
Pereson S; Wils H; Kleinberger G; McGowan E; Vandewoestyne M; Van Broeck B; Joris G; Cuijt I; Deforce D; Hutton M; Van Broeckhoven C; Kumar-Singh S. 2009. Progranulin expression correlates with dense-core amyloid plaque burden in Alzheimer disease mouse models. J Pathol 219(2):173-81. [PubMed: 19557827] [MGI Ref ID J:154721]
Stokin 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
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry Mutant mice were bred to C57BL/6J mice to generate this congenic strain. When maintaining the live congenic colony, hemizygous mice are bred with wildtype siblings or to C57BL/6J inbred mice.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|
|
|
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Payment Terms and Conditions
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
See Terms of Use tab for General Terms and Conditions
The Jackson Laboratory's Genotype Promise
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.Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form
Terms of Use
Terms of Use
General Terms and Conditions
For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.
Contact information
General inquiries regarding Terms of UseContracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.
No Liability
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.