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| These transgenic mice carry a humanized synuclein (alpha-syn) mutant (SNCA*A53T) gene regulated by a tetracycline operator (tetO). When mated to a mutant strain expressing tTA, expression of SNCA*A53T protein may be regulated with the tetracycline analog doxycycline in the double mutant offspring. | |||||||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Former Names C57BL/6J-Tg(tetO-SNCA*A53T)E2Cai/J (Changed: 22-SEP-11 ) Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Huaibin Cai, NIA Description
Mice hemizygous for the human synuclein (alpha-syn) mutant transgene, (SNCA*A53T) are viable and fertile. Expression of SNCA*A53T is regulated by the tetracycline operator (tetO); also called tetracycline-responsive element (TRE, TetRE) or tet-operator). When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of SNCA*A53T protein may be regulated with tetracycline or its analog doxycycline (dox) in the double mutant offspring. Mutations in alpha-syn greatly accelerate the formation of fibrillar aggregates causing various forms of cytotoxicity, including impairment of proteasomal and lysosomal activities, disruption of ER-Golgi traffic and microtubule-based transport, and dysfunction of mitochondria. SNCA*A53T mice develop age-dependent, progressive neurodegeneration. These mice may be useful for studying the Parkinson's disease pathogenesis and neurodegeneration elicited by the toxic effects of aggregation and somatic accumulation of SNCA.Development
A transgene was generated encoding a human SNCA*A53T mutant gene under control of a tetO promoter. The construct was microinjected into C57BL/6J fertilized oocytes, and founder mice were bred to C57BL/6J mice to establish a colony. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.A 32 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory revealed 10 of 32 markers (on six different chromosomes) that were not C57BL/6J allele-type. These data suggest C57BL/6N, FVB, and/or other genetic contamination prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
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| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Related Strains
Parkinson's Disease Models
View Parkinson's Disease Models (99 strains)
Additional Web Information
Tet Expression Systems
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
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-SNCA*A53T)E2Cai/0
involves: C57BL/6
- growth/size phenotype
- decreased body weight
- A53T mice weigh significantly less than non transgenic mice and Tg(tetO-SNCA*A53T)E2Cai or Tg(Camk2a-tTA)1Mmay single mutants starting at 4 months of age (MGI Ref ID J:156512)
- behavior/neurological phenotype
- abnormal locomotor activation (MGI Ref ID J:156512)
- nervous system phenotype
- abnormal nervous system morphology
- only a few neurons in the brain display alpha-synuclein staining in the cell body at 3 months; somatic accumulation becomes more prominent at 20 months; whereas no accumulation is detected in cell bodies at 1 month (MGI Ref ID J:156512)
- significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (MGI Ref ID J:156512)
- abnormal cerebral cortex morphology
- abnormal neuron morphology
- the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented (MGI Ref ID J:156512)
- significant increase in Golgi fragmentation is observed at 6 months (MGI Ref ID J:156512)
- at 1 month, the medial/trans-Golgi in neurons is significantly altered with ratio of fragmented trans-Golgi significantly increased compared to non-transgenic animals (MGI Ref ID J:156512)
- significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (MGI Ref ID J:156512)
- abnormal striatum morphology
- alpha-synuclein inclusion body
- a significant increase in detergent-insoluble high molecular weight (HMW) alpha synuclein is detected in 12 month old mice compared to 1 month old mice (MGI Ref ID J:156512)
- significant decrease in HMW alpha-synuclein in total brain homogenates is observed when animals are treated with doxycycline to inhibit transgene expression (MGI Ref ID J:156512)
- astrocytosis
- microgliosis
- abnormal nervous system physiology
- while 3-month old A53T mice show no abnormal neuropathology, but neuropathology is evident at 12 and 20 months (MGI Ref ID J:156512)
- in 6 month old mice, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons; at 20 monts, a punctate staining pattern at neuronal processes is observed (MGI Ref ID J:156512)
- brain homogenates contain significantly elevated levels of ubiquitinated proteins at 3 months (MGI Ref ID J:156512)
- neurodegeneration
- widespread degeneration is observed at 20 months (MGI Ref ID J:156512)
- age-dependent, progressive neurodegeneration occurs (MGI Ref ID J:156512)
- neuronal loss is detected in the frontal cortex (>80%) and dorsal striatum (>74%) at 20 months (MGI Ref ID J:156512)
- a significant reduction (>30%) of striatal neurons is seen at 6 months (MGI Ref ID J:156512)
- hematopoietic system phenotype
- microgliosis
- immune system phenotype
- microgliosis
- cellular phenotype
- abnormal mitochondrial morphology
- in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to non-transgenic controls; these mitochondria are not functional (MGI Ref ID J:156512)
This mouse can be used to support research in many areas including:
Neurobiology Research
Neurodegeneration
Parkinson's Disease
synuclein mutants
Tet Expression System
tTA/rtTA Responsive Strains
Research Tools
Tet Expression Systems
tTA/rtTA Responsive Strains
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(tetO-SNCA*A53T)E2Cai | ||
|---|---|---|---|
| Allele Name | transgene insertion E2, Huaibin Cai | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | alpha-syn A53T; tetO-A53T; | ||
| Mutation Made By | Huaibin Cai, NIA | ||
| Strain of Origin | C57BL/6J | ||
| Expressed Gene | SNCA, synuclein, alpha (non A4 component of amyloid precursor), human | ||
| Promoter | tetO, tet operator, | ||
| Molecular Note | A transgenic vector was generated encoding a human SNCA*A53T mutant gene under control of a tetO promoter. The construct was microinjected into C57BL/6J fertilized oocytes, and founder mice were bred to C57BL/6J mice to establish the E2 line. [MGI Ref ID J:156512] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(tetO-SNCA*A53T), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Lin X; Parisiadou L; Gu XL; Wang L; Shim H; Sun L; Xie C; Long CX; Yang WJ; Ding J; Chen ZZ; Gallant PE; Tao-Cheng JH; Rudow G; Troncoso JC; Liu Z; Li Z; Cai H. 2009. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein. Neuron 64(6):807-27. [PubMed: 20064389] [MGI Ref ID J:156512]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.Colony Maintenance
Breeding & Husbandry When maintained as a live colony, homozygous mice may be bred together or transgene carrier mice may be bred to wild type siblings.
Purchasing information
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
- Cryorecovery - Standard.
We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2574.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
- Cryorecovery - Standard.
We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
General Supply Notes
- This strain is included in the Induced Mutant Resource Colony collection.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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 Information
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