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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.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax
MMRRC Stock Number 034845. 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
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Description
Strain Information
Former Names B6.Cg-Tg(tetO-APPSwInd)102Dbo/J (Changed: 11-AUG-11 ) 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 N11+pN1
Generation DefinitionsDonating Investigator Dr. David R. Borchelt, McKnight Brain Inst, Univ of Florida Description
Hemizygotes for this tetO-APPswe/ind transgene are viable and fertile. These transgenic mice express a chimeric mouse/human amyloid precursor protein (APP695) bearing the Swedish (KM570/571NL) and Indiana (V617F) mutations associated with Alzheimer's disease (APP695swe/ind) under the control of a tetracycline-responsive promoter element (TRE; tetO). When hemizygotes are bred with another transgenic mouse expressing either reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) under the control of a tissue-specific promoter, APP695swe/ind expression in the appropriate tissues of the bitransgenic offspring can be regulated with the tetracycline analog doxycycline (dox). These tetO-APPswe/ind transgenic mice may be useful in studies of Alzheimer's disease and other neurodegenerative diseases.For example, when bred to a strain expressing tTA in brain tissues (Tg(Camk2a-tTA)1Mmay), bi-transgenic offspring show 10-30 fold greater transgenic APP695swe/ind protein expression than endogenous levels and nearly complete suppression following dox treatment. The donating investigators report some differences in APP695swe/ind expression in bi-transgenic offspring dependent upon which APP695swe/ind founder line was used; line 885 (B6.Cg-Tg(tetO-APPSwInd)885Dbo/Mmjax) shows the highest APP695swe/ind expression with greater dox requirements for transgene suppression, line 102 (B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax) has the greatest sensitivity to dox, and line 107 (B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax) and line 18 are similarly intermediate.
Note that tet alone may affect neuronal degeneration and behavioral phenotypes, depending on the genetic background used (see Han et al, J. Neurosci., 2012).
In an attempt to offer alleles on well-characterized or multiple genetic 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 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 (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 102) 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
Alzheimer's Disease Models
View Alzheimer's Disease Models (107 strains)
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
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(tetO-APPSwInd)102Dbo/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)102Dbo/0
involves: C3H/HeJ * C57BL/6 * CBAThis mouse can be used to support research in many areas including:
Tg(tetO-APPSwInd)102Dbo relatedNeurobiology Research
Alzheimer's Disease
strains expressing mutant APP
Neurodegeneration
Tet Expression System
tTA/rtTA Responsive Strains
Research Tools
Neurobiology Research
Tetop Tet System
Tet Expression Systems
tTA/rtTA Responsive Strains
Neurobiology Research
Alzheimer's Disease
inducible models
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(tetO-APPSwInd)102Dbo | ||
|---|---|---|---|
| Allele Name | transgene insertion 102, David R Borchelt | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | tet-APPswe/ind (line 102); tet-APPswe/ind line 102; | ||
| Mutation Made By | Dr. David Borchelt, McKnight Brain Inst, Univ of Florida | ||
| Strain of Origin | (C57BL/6J x C3H/HeJ)F1 | ||
| Expressed Gene | APP695, amyloid beta (A4) precursor protein (chimeric), mouse/human chimera | ||
| Promoter | tetO, tet operator, | ||
| Molecular Note | The mouse amyloid beta (A4) precursor protein (APP) sequence was modified to contain a humanized amyloid-beta (Abeta) domain. This mouse/human chimeric APP (mo/huAPP695 or APP695) was mutated to incorporate the Swedish (KM570/571NL) and Indiana (V617F) APP mutations associated with Alzheimer's disease. This APP695swe/ind sequence was placed downstream of the tetracycline-responsive (TRE or tetO) promoter and mouse prion protein exons 1-2. Line 102 was established. When mice are crossed with a line expressing a tTA transgene, these mice show the greatest doxycycline sensitivity for transgene suppression. [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)102Dbo 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]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintained as a live colony, hemizygous mice are bred to C57BL/6J or wildtype siblings.
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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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
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