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- 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 and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Hemizygote x Hemizygote (Female x Male) 03-JAN-07 Species laboratory mouse Generation N?+N7F4 (01-JAN-09)
Generation DefinitionsDonating 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
Parkinson's Disease Models
View Parkinson's Disease Models (99 strains)
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.
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
assigned by genotype
Tg(Prnp-SNCA*A53T)83Vle/0
involves: C3H * C57BL/6
- behavior/neurological phenotype
- abnormal motor capabilities/coordination/movement
- 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 (MGI Ref ID J:76657)
- nervous system phenotype
- abnormal nervous system morphology
- 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 (MGI Ref ID J:76657)
Tg(Prnp-SNCA*A53T)83Vle/Tg(Prnp-SNCA*A53T)83Vle
involves: C3H * C57BL/6
- mortality/aging
- premature death (MGI Ref ID J:76657)
- growth/size phenotype
- weight loss
- by 8 months of age, begin to lose weight (MGI Ref ID J:76657)
- behavior/neurological phenotype
- abnormal motor capabilities/coordination/movement (MGI Ref ID J:76657)
- abnormal gait
- reduced ambulation by 8 months of age (MGI Ref ID J:76657)
- akinesia
- 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 (MGI Ref ID J:76657)
- hunched posture
- develop hunched backs by 8 months of age (MGI Ref ID J:76657)
- impaired righting response
- unable to right themselves when placed on their sides (MGI Ref ID J:76657)
- paresis
- partial paralysis of limbs is observed by 8 months of age, beginning at a hindleg but affecting all limbs within a few days (MGI Ref ID J:76657)
- tremors
- temulous motion is seen in some mice, possibly related to attempted muscular activity (MGI Ref ID J:76657)
- weakness
- eventually are unable to stand up and support their own body weight (MGI Ref ID J:76657)
- aphagia
- over time become unable to feed themselves (MGI Ref ID J:76657)
- decreased grooming behavior
- by 8 months of age, grooming is neglected (MGI Ref ID J:76657)
- nervous system phenotype
- abnormal myelination
- following axonal degeneration, the myelin sheath loosens and unravels (MGI Ref ID J:76657)
- abnormal spinal nerve morphology
- endoneurial space is increased and axons are filled with vacuoles in the ventral roots of aged mice (MGI Ref ID J:76657)
- alpha-synuclein inclusion body
- 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 (MGI Ref ID J:76657)
- gliosis
- astrocytic gliosis (MGI Ref ID J:76657)
- neurodegeneration
- show signs of neurodegeneration by 8 months of age and develop neurodegenerative disease within 16 months of age (MGI Ref ID J:76657)
- axon degeneration
- significant axonal degeneration in aged mice (MGI Ref ID J:76657)
- muscle phenotype
- abnormal gastrocnemius morphology
- exhibit sparse neurogenic muscle atrophy (MGI Ref ID J:76657)
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 provided by MGI
| 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; PrP-alpha-syn mice (line M83); Tg(SNCA)83Vle; alphaS+; | ||
| 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
Tg(Prnp-SNCA*A53T)83Vle, Standard PCR
Tlr4Lps-d EP, End Point Analysis
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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 relatedBeaudoin GM 3rd; Schofield CM; Nuwal T; Zang K; Ullian EM; Huang B; Reichardt LF. 2012. Afadin, a ras/rap effector that controls cadherin function, promotes spine and excitatory synapse density in the hippocampus. J Neurosci 32(1):99-110. [PubMed: 22219273] [MGI Ref ID J:179366]
Ben Gedalya T; Loeb V; Israeli E; Altschuler Y; Selkoe DJ; Sharon R. 2009. Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling. Traffic 10(2):218-34. [PubMed: 18980610] [MGI Ref ID J:150319]
Clinton LK; Blurton-Jones M; Myczek K; Trojanowski JQ; LaFerla FM. 2010. Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline. J Neurosci 30(21):7281-9. [PubMed: 20505094] [MGI Ref ID J:160821]
Emmanouilidou E; Elenis D; Papasilekas T; Stranjalis G; Gerozissis K; Ioannou PC; Vekrellis K. 2011. Assessment of alpha-synuclein secretion in mouse and human brain parenchyma. PLoS One 6(7):e22225. [PubMed: 21779395] [MGI Ref ID J:175787]
Emmer KL; Waxman EA; Covy JP; Giasson BI. 2011. E46K human alpha-synuclein transgenic mice develop Lewy-like and tau pathology associated with age-dependent, detrimental motor impairment. J Biol Chem 286(40):35104-18. [PubMed: 21846727] [MGI Ref ID J:177590]
Gao 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]
Graham DR; Sidhu A. 2010. Mice expressing the A53T mutant form of human alpha-synuclein exhibit hyperactivity and reduced anxiety-like behavior. J Neurosci Res 88(8):1777-83. [PubMed: 20077428] [MGI Ref ID J:162178]
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]
Israeli E; Yakunin E; Zarbiv Y; Hacohen-Solovich A; Kisos H; Loeb V; Lichtenstein M; Ben-Gedalya T; Sabag O; Pikarsky E; Lorberboum-Galski H; Sharon R. 2011. alpha-Synuclein Expression Selectively Affects Tumorigenesis in Mice Modeling Parkinson's Disease. PLoS One 6(5):e19622. [PubMed: 21611169] [MGI Ref ID J:172735]
Lim Y; Kehm VM; Li C; Trojanowski JQ; Lee VM. 2010. Forebrain overexpression of alpha-synuclein leads to early postnatal hippocampal neuron loss and synaptic disruption. Exp Neurol 221(1):86-97. [PubMed: 19833127] [MGI Ref ID J:156801]
Loeb V; Yakunin E; Saada A; Sharon R. 2010. The transgenic overexpression of alpha-synuclein and not its related pathology associates with complex I inhibition. J Biol Chem 285(10):7334-43. [PubMed: 20053987] [MGI Ref ID J:160720]
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]
Ramsey CP; Tsika E; Ischiropoulos H; Giasson BI. 2010. DJ-1 deficient mice demonstrate similar vulnerability to pathogenic Ala53Thr human alpha-syn toxicity. Hum Mol Genet 19(8):1425-37. [PubMed: 20089532] [MGI Ref ID J:158368]
Sotiriou E; Vassilatis DK; Vila M; Stefanis L. 2010. Selective noradrenergic vulnerability in alpha-synuclein transgenic mice. Neurobiol Aging 31(12):2103-14. [PubMed: 19152986] [MGI Ref ID J:168294]
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]
Wills J; Credle J; Haggerty T; Lee JH; Oaks AW; Sidhu A. 2011. Tauopathic changes in the striatum of A53T alpha-synuclein mutant mouse model of Parkinson's disease. PLoS One 6(3):e17953. [PubMed: 21445308] [MGI Ref ID J:171676]
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) 03-JAN-07 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $261.00 Female or Male Hemizygous for Tg(Prnp-SNCA*A53T)83Vle $320.00 Female or Male Homozygous for Tg(Prnp-SNCA*A53T)83Vle
Pairs /Price (US dollars $) Pair Genotype $522.00 Hemizygous for Tg(SNCA)83Vle x Hemizygous for Tg(SNCA)83Vle Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order 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.
| Pricing for International shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $339.30 Female or Male Hemizygous for Tg(Prnp-SNCA*A53T)83Vle $416.00 Female or Male Homozygous for Tg(Prnp-SNCA*A53T)83Vle
Pairs /Price (US dollars $) Pair Genotype $678.60 Hemizygous for Tg(SNCA)83Vle x Hemizygous for Tg(SNCA)83Vle Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order 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.
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|
Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order 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.
General Supply Notes
- This strain is included in the Induced Mutant Resource Colony collection.
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100010 B6C3F1/J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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