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| These tetO-MAPT*P301L (rTg4510) transgenic mice may be useful in studying the formation of neurofibrillary tangles associated with the progression of Alzheimer's disease. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
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- References
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Description
Strain Information
Former Names FVB-Tg(tetO-MAPT*P301L)#Kha/J (Changed: 05-JUN-12 ) Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Noncarrier x Hemizygote (Female x Male) 20-OCT-11 Mating System Hemizygote x Noncarrier (Female x Male) 20-OCT-11 Species laboratory mouse Generation ?pN1+ (20-FEB-12)
Generation DefinitionsDonating Investigator Dr. Karen K. Hsiao Ashe, University of Minnesota Donating Investigator Dr. Jada Lewis, Center for Translational Research in Neurodegenerative Disease Donating Investigator Dr. Michael Hutton, Mayo Clinic Description
The tetO-MAPT*P301L transgene contains a tetracycline operator (tetO) driving expression of the human four-repeat microtubule-associated protein tau (MAPT) gene. The transgene also contains the frontotemporal dementia-associated P301L mutation sequences (tauP310L) and untranslated sequence from the mouse prion protein gene (Prnp) driving transgene expression in the brain. Homozygous mice are not viable. When mated to a mutant strain expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA), expression of tauP301L protein may be regulated with the tetracycline analog doxycycline (dox) in the double mutant offspring.When bred to mice expressing tTa under regulatory control of the forebrain-specific calcium-calmodulin-dependent kinase II (Camk2a) promoter (see Stock No. 003010), bitransgenic mice expressing approximately 13 units of transgene exhibit age-independent behavioral and pathological abnormalities, as well as age-dependent functional and structural abnormalities, associated with the progression of Alzheimer's disease. After treatment with dox, neuronal death ceases and the ability to acquire and retain new spatial memories is restored.
Development
The tetO-MAPT*P301L transgene was designed with the human four-repeat microtubule-associated protein tau (MAPT), lacking the amino terminal sequence (4R0N) and containing the frontotemporal dementia-associated P301L mutation sequences. Expression of this tauP310L gene was driven by a tetracycline operator (tetO) upstream of a cytomegalovirus minimal promoter, and contained exons 2-3 of the mouse prion protein gene (prnp) untranslated sequence. This transgene was microinjected into fertilized FVB/NCrl oocytes. The resulting mice were bred with FVB/NCrl mice to establish the colony. Upon arrival, transgenic mice were bred with FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish this colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (107 strains)
Additional Web Information
Tet Expression Systems
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
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Frontotemporal Dementia; FTD (MAPT)
Parkinson Disease, Late-Onset; PD (MAPT)
Parkinson-Dementia Syndrome (MAPT)
Pick Disease of Brain (MAPT)
Supranuclear Palsy, Progressive, 1; PSNP1 (MAPT)
assigned by genotype
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-MAPT*P301L)#Kha/0
involves: 129/Sv * C57BL/6 * CBA * FVB/N
- nervous system phenotype
- abnormal dentate gyrus morphology
- progressive atrophy of dentate granule cells (MGI Ref ID J:185792)
- hippocampal neuron degeneration
- progressive atrophy of hippocampal pyramidal neurons (MGI Ref ID J:185792)
Tg(Camk2a-tTA)1Mmay/? Tg(tetO-MAPT*P301L)#Kha/?
involves: 129S6/SvEvTac * FVB/N
- nervous system phenotype
- abnormal forebrain morphology
- gross atrophy of the forebrain was evident in a 10-month-old mouse (MGI Ref ID J:99626)
- abnormal hippocampus CA1 region morphology
- decreased hippocampus pyramidal cell number
- abnormal neuron morphology
- decreased brain weight
- neurofibrillary tangles
- behavior/neurological phenotype
- abnormal spatial learning
- he retention of spatial memory examined by the Morris water maze were impaired as the mice aged (MGI Ref ID J:99626)
- deficit in spatial navigation was also seen in younger mice (MGI Ref ID J:99626)
- the performance improved when treated with doxycycline at 2.5 month-old or at 5.5 month-old (MGI Ref ID J:99626)
This mouse can be used to support research in many areas including:
MAPT relatedNeurobiology Research
Alzheimer's Disease
Tau (Mapt) mutants
inducible models
Neurodegeneration
Tet Expression System
tTA/rtTA Responsive Strains
Research Tools
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Tetop Tet System
Neurobiology Research
Tetop Tet System
Neurobiology Research
Alzheimer's Disease
Parkinson's Disease
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(tetO-MAPT*P301L)#Kha | ||
|---|---|---|---|
| Allele Name | transgene insertion, Karen Hsiao Ashe | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | Tg(tetO-TauP301L)4510; rTg4510; | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | MAPT, microtubule-associated protein tau, human | ||
| Promoter | tetO, tet operator, | ||
| Molecular Note | The human four-repeat tau gene lacking the amino-terminal sequences (4R0N) containing the frontotemporal dementia-associated P301L mutation sequence was placed downstream of the tetracycline-responsive (TRE or tetO) promoter and inserted into the contextof the mouse prion protein gene (prnp) exons 2-3 transcribed but untranslated sequences. When mice are crossed with a line expressing a tTA transgene, Tg(Camk2a-tTA)1Mmay, these mice show the doxycycline sensitivity for transgene suppression. At leasttwo bitransgenic lines were established that can be suppressed with doxycycline. One bitransgenic mouse strain expressing approximately 13 units of tauP301L transgene was named rTg(tau P301L)4510 and was analyzed further. [MGI Ref ID J:99626] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(tetO-MAPT*P301L)#Kha-alternate1, Melt Curve Analysis
Tg(tetO-MAPT*P301L)#Kha-alternate1, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Liu L. 2012. Trans-Synaptic spread of Tau pathology In Vivo PLoS ONE 7(2):e31302. [MGI Ref ID J:179960]
Santacruz K; Lewis J; Spires T; Paulson J; Kotilinek L; Ingelsson M; Guimaraes A; DeTure M; Ramsden M; McGowan E; Forster C; Yue M; Orne J; Janus C; Mariash A; Kuskowski M; Hyman B; Hutton M; Ashe KH. 2005. Tau suppression in a neurodegenerative mouse model improves memory function. Science 309(5733):476-81. [PubMed: 16020737] [MGI Ref ID J:99626]
Additional References
Tg(tetO-MAPT*P301L)#Kha relatedDuBoff B; Gotz J; Feany MB. 2012. Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron 75(4):618-32. [PubMed: 22920254] [MGI Ref ID J:188334]
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]
Kopeikina KJ; Carlson GA; Pitstick R; Ludvigson AE; Peters A; Luebke JI; Koffie RM; Frosch MP; Hyman BT; Spires-Jones TL. 2011. Tau accumulation causes mitochondrial distribution deficits in neurons in a mouse model of tauopathy and in human Alzheimer's disease brain. Am J Pathol 179(4):2071-82. [PubMed: 21854751] [MGI Ref ID J:176290]
Larson ME; Sherman MA; Greimel S; Kuskowski M; Schneider JA; Bennett DA; Lesne SE. 2012. Soluble alpha-Synuclein Is a Novel Modulator of Alzheimer's Disease Pathophysiology. J Neurosci 32(30):10253-66. [PubMed: 22836259] [MGI Ref ID J:186543]
Ljungberg MC; Ali YO; Zhu J; Wu CS; Oka K; Zhai RG; Lu HC. 2012. CREB-activity and nmnat2 transcription are down-regulated prior to neurodegeneration, while NMNAT2 over-expression is neuroprotective, in a mouse model of human tauopathy. Hum Mol Genet 21(2):251-67. [PubMed: 22027994] [MGI Ref ID J:179018]
Rocher AB; Crimins JL; Amatrudo JM; Kinson MS; Todd-Brown MA; Lewis J; Luebke JI. 2010. Structural and functional changes in tau mutant mice neurons are not linked to the presence of NFTs. Exp Neurol 223(2):385-93. [PubMed: 19665462] [MGI Ref ID J:162373]
Vanderweyde T; Yu H; Varnum M; Liu-Yesucevitz L; Citro A; Ikezu T; Duff K; Wolozin B. 2012. Contrasting Pathology of the Stress Granule Proteins TIA-1 and G3BP in Tauopathies. J Neurosci 32(24):8270-83. [PubMed: 22699908] [MGI Ref ID J:185575]
Yue M; Hanna A; Wilson J; Roder H; Janus C. 2011. Sex difference in pathology and memory decline in rTg4510 mouse model of tauopathy. Neurobiol Aging 32(4):590-603. [PubMed: 19427061] [MGI Ref ID J:173738]
de Calignon A; Fox LM; Pitstick R; Carlson GA; Bacskai BJ; Spires-Jones TL; Hyman BT. 2010. Caspase activation precedes and leads to tangles. Nature 464(7292):1201-4. [PubMed: 20357768] [MGI Ref ID J:159296]
de Calignon A; Polydoro M; Suarez-Calvet M; William C; Adamowicz DH; Kopeikina KJ; Pitstick R; Sahara N; Ashe KH; Carlson GA; Spires-Jones TL; Hyman BT. 2012. Propagation of tau pathology in a model of early Alzheimer's disease. Neuron 73(4):685-97. [PubMed: 22365544] [MGI Ref ID J:182498]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX18
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to wildtype (non-carrier) mice from the colony or to FVB/NJ inbred mice (Stock No. 001800). Mating System Noncarrier x Hemizygote (Female x Male) 20-OCT-11 Hemizygote x Noncarrier (Female x Male) 20-OCT-11 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Hemizygous for Tg(tetO-MAPT*P301L)#Kha
Price per Pair (US dollars $) Pair Genotype $302.00 Hemizygous for Tg(tetO-MAPT*P301L)#Kha x Noncarrier $302.00 Noncarrier x Hemizygous for Tg(tetO-MAPT*P301L)#Kha Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Hemizygous for Tg(tetO-MAPT*P301L)#Kha
Price per Pair (US dollars $) Pair Genotype $392.60 Hemizygous for Tg(tetO-MAPT*P301L)#Kha x Noncarrier $392.60 Noncarrier x Hemizygous for Tg(tetO-MAPT*P301L)#Kha Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
|
|
|
Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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