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Strain Name:

C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J

Stock Number:

005706

Availability:

Repository-Cryopreserved

Price and Supply Information

General Terms and Conditions
Additional Licensing and Use Restrictions

Genes & Alleles   CDK5R1;   GFP;   Tg(tetO-CDK5R1/GFP)337Lht;   tetO;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Strain
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Donating Investigator Li-Huei Tsai,   Massachusetts Institue of Technology

Strain 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.

Strain 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.

Mammalian Phenotype Terms 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

Gene & Allele Details

Allele Symbol Tg(tetO-CDK5R1/GFP)337Lht
Allele Name transgene insertion 337, Li-Huei Tsai
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 OriginC57BL/6J
Site of ExpressionWhen 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. 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]

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for JAX® GEMM® Strains

Genotyping Protocols

Fluorescent Proteins (Generic GFP)

Colony Maintenance

Breeding & HusbandryWhen 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.

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Strains carrying other alleles of CDK5R1
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View Strains carrying other alleles of CDK5R1     (1 strain)

Strains carrying other alleles of GFP
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005418   STOCK Tg(HIST1H2BB/EGFP)1Pa/J
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View Strains carrying other alleles of tetO     (26 strains)

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.

Research Applications

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

Developmental 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)

GFP related

Research Tools
Fluorescent Proteins

Tg(tetO-CDK5R1/GFP)337Lht related

Neurobiology Research
Alzheimer's Disease (inducible models)

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

Price and Supply Information

Strain Name: C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J
Stock Number: 005706

Price Details

IMPORTANT NOTE: Prices are based on shipping destination. The shipping destinations are:

*Pricing for Shipping Destination selected:

        International

Price(s) in US dollars ($)
Cryorecovery Fee $2470.00
Cryopreserved Embryos Fee $2080.00

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to the Supply Notes for further information.
Supply Notes Cryopreserved Embryos
This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page.
Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
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 tetO-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.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.
View Control Pricing Information for JAX® Strains.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

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.

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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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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