Strain Name: |
B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J |
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Stock Number: |
007002 |
Availability: | Repository- Live |
General Terms and Conditions |
| Genes & Alleles | APP695; ITM2B; Prnp; Tg(Prnp-ITM2B/APP695*42)A12Emcg; |
Type JAX® GEMM® Strain - Mutant Stock Additional information on JAX® GEMM® Strains. 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 ?+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 |
Mammalian Phenotype Terms assigned by genotype |
| 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 | ||
|---|---|---|
| Noncarrier | (approximate) | |
| Considerations for Choosing Controls | ||
| 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 |
Strains carrying other alleles of APP695
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)
Strains carrying other alleles of Prnp
View Strains carrying other alleles of Prnp (18 strains)
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Room Number AX11
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
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]
| Strain Name: | B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J |
| Stock Number: | 007002 |
IMPORTANT NOTE: Prices are based on shipping destination. To view prices, select your shipping destination.
| 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. |
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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