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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Li-Huei Tsai, Massachusetts Institue of Technology Description
Hemizygous transgenic mice are viable, fertile, normal in size and do not display any behavioral abnormalities. Mice homozygous for this transgene may not be viable. When these transgenic mice are bred with mice expressing the tetracycline-controlled transactivator protein (tTA) under the regulation of a tissue-specific promoter, expression of the CDK5R1/GFP fusion protein in the appropriate tissue of the bitransgenic offspring can be regulated by doxycycline administration. These mice may be useful in studies of Alzheimer's disease and other neurodegenerative tauopathies, amyotrophic lateral sclerosis (ALS), Niemann Pick Type C (NPC) disease, and Parkinson's disease.Note: this transgenic strain was designed to breed with Tg(Camk2a-tTA) transgenic mice, (Stock No. 003010), a transgenic strain that expresses tTA in forebrain neurons. The resulting bitransgenic offspring exhibit the hallmark phenotype of Alzheimer's disease; elevated p25/Cdk5 related hyperphosporylation of tau leading to compromised tau function and progressive tau aggregation.
Development
A transgenic vector was generated encoding the carboxy terminal proteolytic fragment (p25) of human cyclin-dependent kinase 5, regulatory subunit 1 sequence (CDK5R1) bearing a carboxy-terminal green fluorescent protein (GFP) tag under control of a tetracycline-responsive promoter element (TRE; tetO). The construct was microinjected into C57BL/6J fertilized embryos which were implanted into FVB foster mothers. Male offspring were bred to C57BL/6J females, and transgene-positive mice (line 337) were backcrossed for more than 20 generations before arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (170 strains)
003753 FVB/N-Tg(Eno2CDK5R1)1Jdm/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
JAX® NOTES, Fall 2006; 503. New Inducible Models of Alzheimer's Disease.
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
assigned by genotype
Tg(tetO-CDK5R1/GFP)337Lht/0
C57BL/6J-Tg(tetO-CDK5R1/GFP)337Lht
- normal phenotype
- no abnormal phenotype detected (MGI Ref ID J:104240)
- hemizygous mice are viable, fertile, show normal size and display no behavioral abnormalities; homozygosity may be lethal
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-CDK5R1/GFP)337Lht/0
involves: C57BL/6J
- growth/size phenotype
- decreased body weight (MGI Ref ID J:104240)
- transgenic mice with transgene expression induced by removal of doxycycline from their food 4-6 weeks postnatal exhibit a slightly decreased body weight compared to control littermates
- nervous system phenotype
- abnormal forebrain morphology (MGI Ref ID J:104240)
- induced transgenic mice at 12 weeks postnatal display significant forebrain atrophy with decrease in forebrain mass
- in transgenic mice induced for 8 and 12 weeks, there is an increase in aggregations of tau protein (insoluble tau) with an increased amount of phosphorylated tau present; at 15 weeks, there is less soluble tau than in wild-type forebrains and similar results are found at 27 weeks of induction
- abnormal hippocampus morphology (MGI Ref ID J:104240)
- brains of transgenic mice induced for 12 weeks show a significant decrease in thickness and neuronal density in the hippocampus compared to controls
- thin cerebral cortex (MGI Ref ID J:104240)
- brains of transgenic mice induced for 12 weeks show a significant decrease in thickness and neuronal density in the cerebral cortex compared to controls; mice induced for 8 or 12 weeks show a 25 or 40% decrease in cortical neuronal density, respectively, whereas wild-type or non-induced transgenic mice had the same neuronal density
- decreased brain weight (MGI Ref ID J:104240)
- transgenic mice with induction of expression of the transgene for different time periods display progressive decrease in brain weight; with induction for 5 weeks there is a 15-20% decrease in brain weight and with more than 12 weeks of induction, the weight decrease is 30%
- gliosis (MGI Ref ID J:104240)
- reactive astrogliosis is increased throughout the cortex and hippocampus of mutants evident by an increase in radial and stellate-shaped astrocytes
- neurofibrillary tangles (MGI Ref ID J:104240)
- neurofibrillary tangle-like pathology is exhibited in brains of transgenic mice induced for 27 weeks; there are numerous intraneuronal and flame-shaped neurons positive for neurofibrillary tangle-specific proteins in the cortex and hippocampus of transgenic mice but not wild-type
- other methosds also identify neurofibrillary tangle-like structures in the cerebral cortex, hippocampus and entorhinal cortex of transgenic mice
- brains of transgenic mice induced for 8 or 12 weeks do not express markers for late stage tangles similar to what is observed in wild-type
This mouse can be used to support research in many areas including:
GFP relatedDevelopmental Biology Research
Internal/Organ Defects (brain)
Mouse/Human Gene Homologs
Alzheimer's
amyotrophic lateral sclerosis (ALS)
Neurobiology Research
Alzheimer's Disease
Amyotrophic Lateral Sclerosis (ALS)
Behavioral and Learning Defects
Neurodegeneration
Parkinson's Disease
Tet Expression System (tTA/rtTA Responsive Strains)
Research Tools
Fluorescent Proteins
Genetics Research (Mutagenesis and Transgenesis: Tetop Tet System)
Neurobiology Research (Tetop Tet System)
Tet Expression Systems (tTA/rtTA Responsive Strains)
Tg(tetO-CDK5R1/GFP)337Lht relatedResearch Tools
Fluorescent Proteins
Neurobiology Research
Alzheimer's Disease (inducible models)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(tetO-CDK5R1/GFP)337Lht | ||
|---|---|---|---|
| Allele Name | transgene insertion 337, Li-Huei Tsai | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | CK-p25 Tg; p25(337); p25-GFP; tetO-p25-GFP; | ||
| Mutation Made By | Li-Huei Tsai, Massachusetts Institue of Technology | ||
| Strain of Origin | C57BL/6J | ||
| Site of Expression | When bred with mice having the tetracycline-controlled transactivator protein (tTA), this transgene can be inducibly expressed in the offspring. GFP acts as a fusion protein tag with CDK5R1 expression products. | ||
| Expressed Gene | CDK5R1, cyclin-dependent kinase 5, regulatory subunit 1 (p35), human | ||
| Expressed Gene | GFP, Green Fluorescent Protein, jellyfish | ||
| Green Fluorescent Protein (GFP), derived from the jellyfish Aequorea victoria, is a versatile reporter molecule which has found use in many biological applications. In some constructs the original molecule has been modified in order to enhance its fluorescence intensity (EGFP, enhanced GFP). When utilized in a transgenic construct, tissue expressing sufficient amounts of GFP will fluoresce when exposed to a 488 nm light source. | |||
| Promoter | tetO, tet operator, | ||
| Molecular Note | The transgene expresses the carboxy-terminal proteolytic fragment (p25) of human cyclin-dependent kinase 5, regulatory subunit 1, bearing a carboxy-terminal green fluorescent protein (GFP) tag, under control of the tetracycline operator. The purpose of the GFP tag is to differentiate immunologically the transgene-encoded p25 from the endogenous p35 protein. [MGI Ref ID J:104240] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Fluorescent Proteins (Generic GFP), MCA, vers. 2
Fluorescent Proteins (Generic GFP), STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Cruz JC; Tseng HC; Goldman JA; Shih H; Tsai LH. 2003. Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40(3):471-83. [PubMed: 14642273] [MGI Ref ID J:104240]
Additional References
Fischer A; Sananbenesi F; Pang PT; Lu B; Tsai LH. 2005. Opposing roles of transient and prolonged expression of p25 in synaptic plasticity and hippocampus-dependent memory. Neuron 48(5):825-38. [PubMed: 16337919] [MGI Ref ID J:107574]
Tg(tetO-CDK5R1/GFP)337Lht relatedFischer A; Sananbenesi F; Wang X; Dobbin M; Tsai LH. 2007. Recovery of learning and memory is associated with chromatin remodelling. Nature 447(7141):178-182. [PubMed: 17468743] [MGI Ref ID J:120919]
Kim D; Nguyen MD; Dobbin MM; Fischer A; Sananbenesi F; Rodgers JT; Delalle I; Baur JA; Sui G; Armour SM; Puigserver P; Sinclair DA; Tsai LH. 2007. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J 26(13):3169-79. [PubMed: 17581637] [MGI Ref ID J:133121]
Sananbenesi F; Fischer A; Qang X; Schrick C; Neve R; Radulovic J; Tsai LH. 2007. A hippocampal Cdk5 pathway regulates extinction of contextual fear Nat Neurosci 10(8):1012-9. [PubMed: 17632506] [MGI Ref ID J:123051]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, transgenic positive siblings are bred. Alternatively, transgenic mice can be bred with C57BL/6J (Stock No. 000664). Transgenic homozygosity may be lethal.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00 Cryopreserved Embryos Fee $1600.00
Additional Supply Details
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00 Cryopreserved Embryos Fee $2080.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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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
Purchasing Information
JAX® Mice Orders
Surgical Services
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
Distribution to for-profit entities is pending approval from the strain donor, Harvard Medical School. However any researcher, whether affiliated with a for-profit or with a not-for-profit entity, whose purpose is to mate these tet0-p25-GFP mice with Camk2a-tTa plus tau and/or APP transgenic mice to create triple transgenic lines will be entitled to get these tetO-p25-GFP mice at cost, as the result of an agreement between Harvard Medical School and the Alzheimer Research Consortium.
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:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
Contact information
General inquiries
Contracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice & Services Conditions of Use
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