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Strain Name:

B6.Cg-Tg(tetO-APPSwInd)107Dbo/J

Stock Number:

007052

Availability:

Repository- Live

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Genes & Alleles   APP695;   Tg(tetO-APPSwInd)107Dbo;   tetO;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Transgenic
Mating SystemHemizygote x +/+ sibling         (Female x Male)
Specieslaboratory mouse
Donating Investigator David Borchelt,   McKnight Brain Inst, Univ of Florida
Generation?+F0 (20-DEC-07)

Strain 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.

Strain 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.

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)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

Gene & Allele Details

Allele Symbol Tg(tetO-APPSwInd)107Dbo
Allele Name transgene insertion 107, David R Borchelt
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]

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, hemizygous mice are bred to C57BL/6J or wildtype siblings.
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying other alleles of APP695     (8 strains)

View Strains carrying other alleles of tetO     (27 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.

Animal Health Reports

Room Number           AX11

Research Applications

This mouse can be used to support research in many areas including:

Mouse/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)

APP695 related

Neurobiology Research
Alzheimer's Disease

Tg(tetO-APPSwInd)107Dbo related

Neurobiology Research
Alzheimer's Disease (inducible models)

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

Price and Supply Information

Strain Name: B6.Cg-Tg(tetO-APPSwInd)107Dbo/J
Stock Number: 007052

Price Details

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Supply Details

Standard SupplyRepository-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.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

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.

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.
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