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| This strain is now distributed by the Mutant Mouse Regional Resource Center. Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for ordering information and strain details on B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/Mmjax
MMRRC Stock Number 034842. As a designated MMRRC center, The Jackson Laboratory will continue to distribute these mice at the same high health and quality standards but ordering is exclusively provided through the MMRRC. | |||||||||||||||||||
| 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
Former Names B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J (Changed: 11-AUG-11 ) Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+N0pN1
Generation DefinitionsDonating Investigator Eileen McGowan, Mayo Clinic College of Medicine
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (108 strains)
007182 B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J
007180 B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J 007182 B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J
007182 B6.Cg-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.
Phenotype
Phenotype Information
assigned by genotype
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)
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, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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 relatedPereson 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
Health & Colony Maintenance Information
Currently there is no information available for this strain. This may be due to the supply level of this strain.
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This strain is currently Transferred.
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