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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Hemizygote x +/+ sibling (Female x Male) Species laboratory mouse Generation ?+F0 (20-DEC-07) 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 in the target tissue of the bitransgenic offspring can be regulated with the tetracycline analog doxycycline (dox) in the resulting double mutant offspring. 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 107) 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 Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of APP695
View Strains carrying other alleles of APP695 (9 strains)
Additional Web Information
Congenic Nomenclature
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
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(tetO-APPSwInd)107Dbo/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)107Dbo/0
involves: C3H/HeJ * C57BL/6 * CBA
- nervous system phenotype
- abnormal astrocyte morphology (MGI Ref ID J:109829)
- activated astrocytes are found near plaques in all affected mice glial pathology is more severe in older mice
- if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity
- abnormal nervous system physiology (MGI Ref ID J:109829)
- mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels
- sensitivity of transgene suppression by doxycycline is intermediate between mice of line 885 and line 102
- CNS inflammation (MGI Ref ID J:109829)
- neuritic pathology is observed around plaques; neuritic pathology is more severe in older mice
- if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity
- amyloid beta deposits (MGI Ref ID J:109829)
- doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels
- early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment
- plaques are restricted to the forebrain, including the cortex, hippocampus, olfactory bulb, and striatum; by 6 months, amyloid burden covers large cortical and hippocampal areas
- first observed plaques are fibrillar-core deposits; in 6 month old animals, diffuse plaques are apparent and these are abundant at 9 months, while in 9-12 month-old mice, plaques are visible in the thalamus
- no lesions are observed in the cerebellum or brain stem
- animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months
- mice raised for 6 months with no (DOX) treatment, followed by 3 or 6 months of DOX treatment show similar pathology to untreated 6-month old animals, despite relatively long lesion clearance times
- neurofibrillary tangles (MGI Ref ID J:109829)
- first visible plaques are fibrillary-cored deposits
- behavior/neurological phenotype
- abnormal circadian rhythm (MGI Ref ID J:109829)
- all animals raised with doxycycline have altered circadian rhythms with less distinction between day- and nighttime activity levels
- abnormal locomotor activation (MGI Ref ID J:109829)
- hyperactive behavior is partially reversed in some mice by 1 month of transgene suppression starting at 4-5 months of age
- hyperactivity (MGI Ref ID J:109829)
- untreated mice show hyperactivity, often running in circles around the perimeter of cages
- similar patterns of activity are observed in Morris water maze, with repetitive swim patterns seen in radial water maze swim test
- hyperactive phenotype penetrance is ~100%
- untreated mice show 10-fold more ambulatory activity during the dark phase; even in light phase, activity is several-fold increased compared to wild-type controls; this activity is completely abolished in mice raised on doxycycline
- immune system phenotype
- CNS inflammation (MGI Ref ID J:109829)
- neuritic pathology is observed around plaques; neuritic pathology is more severe in older mice
- if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity
- other phenotype
- amyloid beta deposits (MGI Ref ID J:109829)
- doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels
- early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment
- plaques are restricted to the forebrain, including the cortex, hippocampus, olfactory bulb, and striatum; by 6 months, amyloid burden covers large cortical and hippocampal areas
- first observed plaques are fibrillar-core deposits; in 6 month old animals, diffuse plaques are apparent and these are abundant at 9 months, while in 9-12 month-old mice, plaques are visible in the thalamus
- no lesions are observed in the cerebellum or brain stem
- animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months
- mice raised for 6 months with no (DOX) treatment, followed by 3 or 6 months of DOX treatment show similar pathology to untreated 6-month old animals, despite relatively long lesion clearance times
This mouse can be used to support research in many areas including:
APP695 relatedMouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease (strains expressing mutant APP)
Alzheimer's Disease
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)107Dbo relatedNeurobiology Research
Alzheimer's Disease
Neurobiology Research
Alzheimer's Disease (inducible models)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(tetO-APPSwInd)107Dbo | ||
|---|---|---|---|
| Allele Name | transgene insertion 107, David R Borchelt | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | tet-APPswe/ind line 107; | ||
| Mutation Made By | 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 107 was established and most thoroughly studied. [MGI Ref ID J:109829] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Generic Tg(APP) Melt Curve Analysis, MCA, vers. 3
Tg(APP), STD PCR, vers. 2
Helpful Links
Optimizing PCR Protocols
References
References
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)107Dbo 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]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintained as a live colony, hemizygous mice are bred to C57BL/6J or wildtype siblings. Mating System Hemizygote x +/+ sibling (Female x Male) Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Hemizygous for Tg(tetO-APPSwInd)107Dbo *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Hemizygous for Tg(tetO-APPSwInd)107Dbo x Noncarrier
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Hemizygous for Tg(tetO-APPSwInd)107Dbo *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Hemizygous for Tg(tetO-APPSwInd)107Dbo x Noncarrier
Additional Supply Details
| Supply Notes |
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Supply Details
| 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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Control Information
| 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. | ||
General Terms and Conditions
See Terms of Use
The Jackson Laboratory's Genotype Promise
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 and Purchasing Information
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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form
Terms of Use
Terms of Use
General Terms and Conditions
Use of the Tet-System may require a license, see Licenses for Strains Using TET-System Technology.
For additional Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.
Contact information
General inquiries
Contracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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