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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 B6C3-Tg(tetO-APPSwInd)885Dbo/Mmjax
MMRRC Stock Number 034834. 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 TetAPPswe/ind mice express human APP bearing the Swedish and Indiana mutations in a tet-responsive manner. Amyloid pathology is observed when the transgene is expressed. This strain has been shown to be useful in studies correlating temporal expression of mutant APP expression with Alzheimer's-like amyloid pathology. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Former Names B6C3-Tg(tetO-APPSwInd)885Dbo/J (Changed: 10-AUG-11 ) B6C3-Tg(tetO-APPSwInd)8-85Dbo/J (Changed: 14-FEB-07 ) B6C3-Tg(tetO-APPswe/ind)8-85Dbo/J (Changed: 13-FEB-07 ) Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+N1p
Generation DefinitionsDonating Investigator Dr. David R. Borchelt, McKnight Brain Inst, Univ of Florida Description
Hemizygous mice are viable and fertile. These transgenic mice express a chimeric mouse/human amyloid precursor protein (APP) bearing the Swedish (KM570/571NL) and Indiana (V617F) mutations associated with Alzheimer's disease (APPswe/ind) under the control of a tetracycline-responsive promoter element (TRE; tetO). When hemizygotes are bred with another transgenic mouse expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) under the regulation of tissue-specific promoters , APPswe/ind transgene expression can be regulated in the appropriate tissue of the bitransgenic offspring with the tetracycline analog, doxycycline.Note that tet alone may affect neuronal degeneration and behavioral phenotypes, depending on the genetic background used (see Han et al, J. Neurosci., 2012).
When bred to a strain expressing rtTA or tTA in brain tissues (B6;CBA-Tg(Camk2a-tTA)1Mmay/J), this mutant mouse strain may be useful in studies of Alzheimer's Disease.
Development
The mouse amyloid beta (A4) precursor protein (App) sequence was first modified to contain a humanized amyloid-beta (Abeta) domain. This mouse/human chimeric APP (called mo/huAPP695 or APP695) was further mutated to incorporate the Swedish (KM570/571NL) and Indiana (V617F) mutations associated with Alzheimer's disease. This APP695swe/ind sequence was placed downstream of the tetracycline-responsive promoter (TRE; tetO) promoter and mouse prion protein exons 1-2. The complete tetracycline-responsive APP695swe/ind transgene (tet-APPswe/ind) was injected into the pronucleus of fertilized eggs from (C57BL/6J x C3HeJ) F1 matings. Transgene positive founders (line 885) were bred to transgenic Camk2a-tTA mice (B6;CBA-Tg(Camk2a-tTA)1Mmay/J) on a B6;CBA mixed genetic background. After 3-4 generations of brother-sister matings, mice harboring only the tet-APPswe/ind transgene were selected and backcrossed to C57BL/6 for at least 10 generations prior to arrival at the MMRRC at The Jackson Laboratory.
Related Strains
Strains carrying Tg(tetO-APPSwInd)885Dbo allele
007049 B6.Cg-Tg(tetO-APPSwInd)885Dbo/Mmjax View Strains carrying Tg(tetO-APPSwInd)885Dbo (1 strain)
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
- 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. Alzheimer Disease; AD (APP)
Cerebral Amyloid Angiopathy, App-Related (APP)
assigned by genotype
Tg(tetO-APPSwInd)885Dbo/0
involves: C3H/HeJ * C57BL/6J
- no phenotypic analysis
- *normal* no phenotypic analysis
- no analysis of single transgenic mice provided (MGI Ref ID J:109829)
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-APPSwInd)885Dbo/0
involves: C3H/HeJ * C57BL/6 * CBA
- nervous system phenotype
- abnormal dentate gyrus morphology
- mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus (MGI Ref ID J:185792)
- abnormal nervous system physiology
- amyloid beta deposits (MGI Ref ID J:185792)
- other phenotype
- amyloid beta deposits (MGI Ref ID J:185792)
This mouse can be used to support research in many areas including:
APP relatedMouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
strains expressing mutant APP
Behavioral and Learning Defects
Tet Expression System
tTA/rtTA Responsive Strains
Research Tools
Neurobiology Research
Tetop Tet System
Tet Expression Systems
tTA/rtTA Responsive Strains
Tg(tetO-APPSwInd)885Dbo relatedMouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
Neurodegeneration
Neurobiology Research
Alzheimer's Disease
inducible models
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(tetO-APPSwInd)885Dbo | ||
|---|---|---|---|
| Allele Name | transgene insertion 885, David R Borchelt | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | TetAPPswe/ind line 885; | ||
| Mutation Made By | Dr. David Borchelt, McKnight Brain Inst, Univ of Florida | ||
| Strain of Origin | (C57BL/6J x C3H/HeJ)F2 | ||
| Expressed Gene | APP, amyloid beta (A4) precursor protein, human | ||
| Promoter | tetO, tet operator, | ||
| General Note | Founder line 8-85 is the highest expressing line, and is representative of a number of lines made with this construct. | ||
| Molecular Note | The transgene expresses the mutant human amyloid protein precursor APPSwInd, which bears both the Swedish (K670N/M671L) and the Indiana (V717F) mutations, under the control of the tetracycline-responsive element (tetO). When bred to another transgenic mouse expressing reverse tertracyclin-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (fTA) to creat a bitransgenic animal, tissue APPSwInd transgene expression can be regulated with the tetracycline analog, doxycycline. These double transgenic show the highest APPSwInd expression and have the highest doxycycline requirements for suppression of transgene expression. [MGI Ref ID J:109829] [MGI Ref ID J:80782] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Generic Tg(APP), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Jankowsky JL; Slunt HH; Gonzales V; Savonenko AV; Wen JC; Jenkins NA; Copeland NG; Younkin LH; Lester HA; Younkin SG; Borchelt DR. 2005. Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease. PLoS Med 2(12):e355. [PubMed: 16279840] [MGI Ref ID J:109829]
Additional References
Tg(tetO-APPSwInd)885Dbo relatedBorchelt DR; Davis J; Fischer M; Lee MK; Slunt HH; Ratovitsky T; Regard J; Copeland NG; Jenkins NA; Sisodia SS; Price DL. 1996. A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal 13(6):159-63. [PubMed: 9117892] [MGI Ref ID J:80782]
Han HJ; Allen CC; Buchovecky CM; Yetman MJ; Born HA; Marin MA; Rodgers SP; Song BJ; Lu HC; Justice MJ; Probst FJ; Jankowsky JL. 2012. Strain background influences neurotoxicity and behavioral abnormalities in mice expressing the tetracycline transactivator. J Neurosci 32(31):10574-86. [PubMed: 22855807] [MGI Ref ID J:185792]
Harris JA; Devidze N; Verret L; Ho K; Halabisky B; Thwin MT; Kim D; Hamto P; Lo I; Yu GQ; Palop JJ; Masliah E; Mucke L. 2010. Transsynaptic progression of amyloid-beta-induced neuronal dysfunction within the entorhinal-hippocampal network. Neuron 68(3):428-41. [PubMed: 21040845] [MGI Ref ID J:167860]
Lin X; Parisiadou L; Gu XL; Wang L; Shim H; Sun L; Xie C; Long CX; Yang WJ; Ding J; Chen ZZ; Gallant PE; Tao-Cheng JH; Rudow G; Troncoso JC; Liu Z; Li Z; Cai H. 2009. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein. Neuron 64(6):807-27. [PubMed: 20064389] [MGI Ref ID J:156512]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as hemizygotes.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
This strain is currently Transferred.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
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