| |||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Former Names B6;C3H-Tg(SNCA)83Vle/J (Changed: 21-MAR-08 ) M83 (Changed: 15-DEC-04 ) Type Mutant Stock; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Hemizygote x Hemizygote (Female x Male) Species laboratory mouse Generation N?+N7F3 (06-DEC-07) Donating Investigator Virginia Lee, University of Pennsylvania Description
Mice homozygous for the transgenic insert are viable and normal in size. These transgenic mice express human A53T variant alpha-synuclein (full-length, 140 amino acid isoform) under the direction of the mouse prion protein promoter. At eight months of age, some homozygous mice develop a progressively severe motor phenotype. Presentation of the phenotype may manifest at 14-15 months of age (on average). Lax grooming, weight loss and diminished mobility precede movement impairment, partial limb paralysis, trembling and inability to stand. Immunohistochemistry analysis of mutants between eight to 12 months of age reveals widely distributed alpha-synuclein inclusions, with dense accumulation in the spinal cord, brainstem, cerebellum and thalamus. The appearance of alpha-synuclein aggregate inclusions parallels the onset of the motor impairment phenotype. Axons and myelin sheaths exhibit progressive ultrastructural degeneration. Immunoelectron microscopy and biochemical analysis show the inclusions in neurons are comprised primarily of 10-16 nm fibrils of alpha-synuclein. The structure, location and onset of the inclusions seen in the mutant mice resemble characteristics seen in human neuronal alpha-synucleinopathies, such as familial Parkinson's Disease. Mice hemizygous for the transgenic insert develop similar phenotypic traits, but onset occurslater, between 22 and 28 months of age. Homozygous mice have a high incidence of nonproductive matings. This mutant mouse strain represents a model that may be useful in studies of Parkinson's Disease.Development
A transgenic construct containing the mouse prion protein promoter, its 5' and 3' untranslated regions and human alpha-synuclein A53T mutation cDNA sequence was injected into fertilized B6C3H mouse eggs. Transgenic animals are maintained on a mixed B6C3H background.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100010 B6C3F1/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Prnp
View Strains carrying other alleles of Prnp (20 strains)
008473 B6.Cg-Tg(THY1-SNCA*A30P)M30Sud/J 008134 B6.Cg-Tg(THY1-SNCA*A30P)TS2Sud/J 008474 B6.Cg-Tg(THY1-SNCA*A53T)F53Sud/J 008135 B6.Cg-Tg(THY1-SNCA*A53T)M53Sud/J 008389 C57BL/6-Tg(THY1-SNCA)1Sud/J
Additional Web Information
JAX® NOTES, Fall 2003; 491. Novel Familial Parkinson's Disease Model.
JAX® NOTES, Summer 2007; 506. New Parkinson's Disease Mouse Model Resource.
Phenotype
Phenotype Information
assigned by genotype
Tg(Prnp-SNCA*A53T)83Vle/0
involves: C3H * C57BL/6
- behavior/neurological phenotype
- abnormal motor capabilities/coordination/movement (MGI Ref ID J:76657)
- develop the severe and complex motor impairment leading to paralysis and death that is seen in homozygous transgenics, however onset is delayed from 16 months of age to 22-28 months of age
- nervous system phenotype
- abnormal nervous system morphology (MGI Ref ID J:76657)
- develop a similar neurodegenerative disease that is observed in homozygous transgenic mice, however onset is delayed from 16 months of age to 22-28 months of age
Tg(Prnp-SNCA*A53T)83Vle/Tg(Prnp-SNCA*A53T)83Vle
involves: C3H * C57BL/6
- life span-post-weaning/aging
- premature death (MGI Ref ID J:76657)
- growth/size phenotype
- weight loss (MGI Ref ID J:76657)
- by 8 months of age, begin to lose weight
- behavior/neurological phenotype
- abnormal motor capabilities/coordination/movement (MGI Ref ID J:76657)
- abnormal gait (MGI Ref ID J:76657)
- reduced ambulation by 8 months of age
- akinesia (MGI Ref ID J:76657)
- by 8 months of age, exhibit severe movement impairment with resistance to passive movement and partial paralysis of limbs, accompanied by periods of freezing of hindlimb
- hunched posture (MGI Ref ID J:76657)
- develop hunched backs by 8 months of age
- impaired righting response (MGI Ref ID J:76657)
- unable to right themselves when placed on their sides
- paresis (MGI Ref ID J:76657)
- partial paralysis of limbs is observed by 8 months of age, beginning at a hindleg but affecting all limbs within a few days
- tremors (MGI Ref ID J:76657)
- temulous motion is seen in some mice, possibly related to attempted muscular activity
- weakness (MGI Ref ID J:76657)
- eventually are unable to stand up and support their own body weight
- aphagia (MGI Ref ID J:76657)
- over time become unable to feed themselves
- decreased grooming behavior (MGI Ref ID J:76657)
- by 8 months of age, grooming is neglected
- nervous system phenotype
- abnormal myelination (MGI Ref ID J:76657)
- following axonal degeneration, the myelin sheath loosens and unravels
- abnormal spinal nerve morphology (MGI Ref ID J:76657)
- endoneurial space is increased and axons are filled with vacuoles in the ventral roots of aged mice
- alpha-synuclein inclusion body (MGI Ref ID J:76657)
- develop age-dependent intracytoplasmic neuronal alpha-synuclein inclusions that contain 10-16 nm wide fibrils similar to those seen in human alpha-synucleinopathies, with dense accumulation in the spinal cord, brainstem, cerebellum, and thalamus
- gliosis (MGI Ref ID J:76657)
- astrocytic gliosis
- neurodegeneration (MGI Ref ID J:76657)
- show signs of neurodegeneration by 8 months of age and develop neurodegenerative disease within 16 months of age
- axon degeneration (MGI Ref ID J:76657)
- significant axonal degeneration in aged mice
- muscle phenotype
- abnormal gastrocnemius morphology (MGI Ref ID J:76657)
- exhibit sparse neurogenic muscle atrophy
This mouse can be used to support research in many areas including:
Neurobiology Research
Neurodegeneration
Parkinson's Disease (synuclein mutants)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Prnp-SNCA*A53T)83Vle | ||
|---|---|---|---|
| Allele Name | transgene insertion 83, Virginia M-Y Lee | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | A53T alpha-synuclein PRP; M83; Tg(SNCA)83Vle; | ||
| Mutation Made By | John Trojanowski, Dept. Pathology and Laboratory Med | ||
| Strain of Origin | C57BL/6 x C3H | ||
| Expressed Gene | SNCA, synuclein, alpha (non A4 component of amyloid precursor), human | ||
| Promoter | Prnp, prion protein, mouse, laboratory | ||
| General Note | This line was originally designated M83. Line M91 was also generated. | ||
| Molecular Note | The transgene contains the mouse prion protein promoter, its 5' and 3' untranslated regions, and a human alpha synuclein cDNA sequence encoding a mutated protein with an Ala53Thr mutation. Transgene expression was detected in the cerebral cortex, spinalcord, and cerebellum. [MGI Ref ID J:76657] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Prnp-SNCA*A53T)83Vle, QPCR, vers. 2
Tg(Prnp-SNCA*A53T)83Vle, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Giasson BI; Duda JE; Quinn SM; Zhang B; Trojanowski JQ; Lee VM. 2002. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34(4):521-33. [PubMed: 12062037] [MGI Ref ID J:76657]
Additional References
Tg(Prnp-SNCA*A53T)83Vle relatedGao HM; Kotzbauer PT; Uryu K; Leight S; Trojanowski JQ; Lee VM. 2008. Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J Neurosci 28(30):7687-98. [PubMed: 18650345] [MGI Ref ID J:138194]
Ihara M; Yamasaki N; Hagiwara A; Tanigaki A; Kitano A; Hikawa R; Tomimoto H; Noda M; Takanashi M; Mori H; Hattori N; Miyakawa T; Kinoshita M. 2007. Sept4, a component of presynaptic scaffold and Lewy bodies, is required for the suppression of alpha-synuclein neurotoxicity. Neuron 53(4):519-33. [PubMed: 17296554] [MGI Ref ID J:136786]
Norris EH; Uryu K; Leight S; Giasson BI; Trojanowski JQ; Lee VM. 2007. Pesticide exposure exacerbates alpha-synucleinopathy in an A53T transgenic mouse model. Am J Pathol 170(2):658-66. [PubMed: 17255333] [MGI Ref ID J:117818]
Uryu K; Richter-Landsberg C; Welch W; Sun E; Goldbaum O; Norris EH; Pham CT; Yazawa I; Hilburger K; Micsenyi M; Giasson BI; Bonini NM; Lee VM; Trojanowski JQ. 2006. Convergence of heat shock protein 90 with ubiquitin in filamentous alpha-synuclein inclusions of alpha-synucleinopathies. Am J Pathol 168(3):947-61. [PubMed: 16507910] [MGI Ref ID J:106557]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry The strain is maintained as a hemizygote on the same background. Homozygous mice have a high incidence of nonproductive matings. Coat color expected from breeding:Agouti. Mating System Hemizygote x Hemizygote (Female x Male) Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Hemizygous for Tg(Prnp-SNCA*A53T)83Vle $236.40 Female or Male Homozygous for Tg(Prnp-SNCA*A53T)83Vle *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $472.80 Hemizygous for Tg(SNCA)83Vle x Hemizygous for Tg(SNCA)83Vle
Additional Supply Details
| Supply Notes |
|
|---|
| Pricing for International shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Hemizygous for Tg(Prnp-SNCA*A53T)83Vle $307.40 Female or Male Homozygous for Tg(Prnp-SNCA*A53T)83Vle *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $614.70 Hemizygous for Tg(SNCA)83Vle x Hemizygous for Tg(SNCA)83Vle
Additional Supply Details
| Supply Notes |
|
|---|
|
|
|
Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100010 B6C3F1/J | (approximate) | |
| 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
For 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
“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”No Warranty
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. THE LABORATORY EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.
No Liability
In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.
MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.
Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.