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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)107Dbo/Mmjax
MMRRC Stock Number 034846. 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 B6.Cg-Tg(tetO-APPSwInd)107Dbo/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 ?+F0pN1
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 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 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 107) 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 (108 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)107Dbo/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)107Dbo/0
involves: C3H/HeJ * C57BL/6 * CBA
- nervous system phenotype
- abnormal astrocyte morphology
- 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
- CNS inflammation
- hippocampal neuron degeneration
- amyloid beta deposits
- doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels (MGI Ref ID J:109829)
- early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment (MGI Ref ID J:109829)
- 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 (MGI Ref ID J:109829)
- 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 (MGI Ref ID J:109829)
- no lesions are observed in the cerebellum or brain stem (MGI Ref ID J:109829)
- animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months (MGI Ref ID J:109829)
- 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 (MGI Ref ID J:109829)
- neurofibrillary tangles
- first visible plaques are fibrillary-cored deposits (MGI Ref ID J:109829)
- behavior/neurological phenotype
- abnormal circadian rhythm
- all animals raised with doxycycline have altered circadian rhythms with less distinction between day- and nighttime activity levels (MGI Ref ID J:109829)
- abnormal locomotor activation
- hyperactive behavior is partially reversed in some mice by 1 month of transgene suppression starting at 4-5 months of age (MGI Ref ID J:109829)
- hyperactivity
- untreated mice show hyperactivity, often running in circles around the perimeter of cages (MGI Ref ID J:109829)
- similar patterns of activity are observed in Morris water maze, with repetitive swim patterns seen in radial water maze swim test (MGI Ref ID J:109829)
- hyperactive phenotype penetrance is ~100% (MGI Ref ID J:109829)
- 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 (MGI Ref ID J:109829)
- immune system phenotype
- CNS inflammation
- other phenotype
- amyloid beta deposits
- doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels (MGI Ref ID J:109829)
- early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment (MGI Ref ID J:109829)
- 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 (MGI Ref ID J:109829)
- 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 (MGI Ref ID J:109829)
- no lesions are observed in the cerebellum or brain stem (MGI Ref ID J:109829)
- animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months (MGI Ref ID J:109829)
- 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 (MGI Ref ID J:109829)
This mouse can be used to support research in many areas including:
Tg(tetO-APPSwInd)107Dbo 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
Neurobiology Research
Alzheimer's Disease
inducible models
Genes & Alleles
Gene & Allele Information provided by MGI
| 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 | 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 107 was established and most thoroughly studied. [MGI Ref ID J:109829] | ||
Genotyping
Genotyping Information
Genotyping Protocols
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)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]
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]
Melnikova T; Fromholt S; Kim H; Lee D; Xu G; Price A; Moore BD; Golde TE; Felsenstein KM; Savonenko A; Borchelt DR. 2013. Reversible pathologic and cognitive phenotypes in an inducible model of Alzheimer-amyloidosis. J Neurosci 33(9):3765-79. [PubMed: 23447589] [MGI Ref ID J:195259]
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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