Strain Name: |
B6;C3-Tg(Prnp-ITM2B/APP695*40)1Emcg/J |
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Stock Number: |
006880 |
Availability: | Repository- Live |
General Terms and Conditions |
| Genes & Alleles | APP695; ITM2B; Prnp; Tg(Prnp-ITM2B/APP695*40)1Emcg; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Mutant Stock Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Targeted Mutation Type JAX® GEMM® Strain - Transgenic Mating System Noncarrier x Hemizygote (Female x Male) Species laboratory mouse Donating Investigator Eileen McGowan, Mayo Clinic College of Medicine Generation N1F0 (03-DEC-07) Strain Description
Mice hemizygous for this BRI-Abeta40 transgene are viable and fertile with a normal life span and no obvious behavioral abnormalities. Transgenic BRI-Abeta mRNA is expressed in a pattern characteristic of the mouse prion protein promoter; highest 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, Abeta1-40 is fused to the C terminus of the BRI protein at the furin-like cleavage site such that cleavage results in efficient Abeta1-40 secretion into the lumen or extracellular space. Therefore, these mice specifically express the Abeta1-40 isoform in the absence of human amyloid beta protein precursor (APP) overexpression. In contrast to BRI-Abeta42 transgenic mice (Stock No. 007002), hemizygous BRI-Abeta40 mice expressing high levels of Abeta1-40 (80-120pm/gm at 3 months of age) neither develop overt amyloid pathology nor accumulate detergent-insoluble amyloid-beta. These mutant mice may be useful in neurological studies of Alzheimer's disease, neurodegeneration, and amyloid plaque formation.Strain Development
The BRI-Abeta40 transgene was generated with a mouse prion promoter upstream of a BRI-Abeta40 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-beta40 (Abeta40) at the furin-like cleavage site; the C-terminal 23 amino acid ABri peptide of BRI was replaced with the Abeta40 sequence. The transgene was injected into the pronuclei of single-cell embryos from C3B6F1 × B6 mice and then implanted into pseudopregnant females. A single founder line with the highest Abeta40 plasma levels, line 1d, was maintained on a mixed B6C3 background prior to arrival at The Jackson Laboratory.
Related Disease (OMIM) Terms |
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Tg(Prnp-ITM2B/APP695*40)1Emcg | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Eileen McGowan | ||
| Common Name(s) | BRI-Abeta1-40; BRI-Abeta40; | ||
| 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 BRI-Abeta40 transgene was generated with a mouse prion promoter upstream of a BRI-Abeta40 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-beta40 (Abeta40) at the furin-like cleavage site; the C-terminal 23 amino acid ABri peptide of BRI was replaced with the Abeta40 sequence. A single founder line with the highest Abeta40 plasma levels (line 1d) was 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 Abeta40 peptide expressed at lower levels. [J:101023] | ||
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100010 B6C3F1/J | (approximate) | |
| Considerations for Choosing Controls | ||
Colony Maintenance
| Breeding & Husbandry | When maintaining a live colony, hemizygous mice can be bred with wildtype littermates or with B6C3F1/J (Stock No. 100010). |
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| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
Strains carrying other alleles of APP695
View Strains carrying other alleles of APP695 (7 strains)
007002 B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J
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:
APP695 relatedMouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease (strains expressing mutant APP)
Alzheimer's Disease
Neurodegeneration
Research Tools
Neurobiology Research
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] [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] [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] [J:101023]
Price and Supply Information
| Strain Name: | B6;C3-Tg(Prnp-ITM2B/APP695*40)1Emcg/J |
| Stock Number: | 006880 |
Price 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 ~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. |
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| Supply Notes |
Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. |
General Terms and Conditions
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For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
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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.Ordering and Purchasing Information
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