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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 N11pN1 Donating Investigator David 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 regulation of a tissue-specific promoter, APP695swe/ind expression can be regulated in the appropriate tissue of the bitransgenic offspring with the tetracycline analog doxycycline (dox). These tetO-APPswe/ind transgenic mice may be useful in studies of Alzheimer's disease and other neurodegenerative tauopathies.For example, when bred to a strain expressing tTA in brain tissues (see Stock No. 007004 or Stock No. 003010), 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 (Stock No. 007049) shows the highest APP695swe/ind expression with greater dox requirements for transgene suppression, line 102 (Stock No. 007051) has the greatest sensitivity to dox, and line 107 (Stock No. 007052) and line 18 are similarly intermediate.
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 885) were bred to transgenic Camk2a-tTA mice (see Stock No. 003010) 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 Jackson Laboratory.
| Control | ||
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| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying Tg(tetO-APPSwInd)885Dbo allele
006004 B6C3-Tg(tetO-APPSwInd)885Dbo/J View Strains carrying Tg(tetO-APPSwInd)885Dbo (1 strain)
Strains carrying other alleles of APP
008609 129S1.129(Cg)-Tg(APPSw)40Btla/2J 006409 129S1.129(Cg)-Tg(APPSw)40Btla/J 006555 A.129(B6)-Tg(APPSw)40Btla/J 005300 B6.129-Tg(APPSw)40Btla/J 005301 B6.129S2-Tg(APP)8.9Btla/J 006406 B6.129S4-Tg(APPSwLon)96Btla/J 009126 B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/J 005864 B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/J 004662 B6.Cg-Tg(PDGFB-APP)5Lms/J 006293 B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2J 006006 B6.Cg-Tg(Prnp-APP)A-2Dbo/J 006005 B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/J 004462 B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J 007027 C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/J 006472 D2.129(B6)-Tg(APPSw)40Btla/J View Strains carrying other alleles of APP (15 strains)
Strains carrying other alleles of tetO
View Strains carrying other alleles of tetO (35 strains)
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(tetO-APPSwInd)885Dbo/0
involves: C3H/HeJ * C57BL/6J
- no phenotypic analysis
- *normal* no phenotypic analysis (MGI Ref ID J:109829)
- no analysis of single transgenic mice provided
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 nervous system physiology (MGI Ref ID J:109829)
- mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels
- expression of APPSw/Ind is higher relative to other three double transgenic lines, and suprression requires more doxycycline than the other three lines
View Research Applications
Research Applications
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
Neurodegeneration
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
| 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 | 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 Protocols
Generic Tg(APP) Melt Curve Analysis, Melt Curve Analysis
Tg(APP), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
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]
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]
Colony Maintenance
Breeding & Husbandry When maintained as a live colony, hemizygous mice are bred to C57BL/6J or wildtype siblings.
| Pricing for USA, Canada and Mexico shipping destinations |
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Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
| Pricing for International shipping destinations |
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Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form
For additional Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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