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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) 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)
008134 B6.Cg-Tg(THY1-SNCA*A30P)TS2Sud/J 008135 B6.Cg-Tg(THY1-SNCA*A53T)M53Sud/J 008473 B6;SJL-Tg(THY1-SNCA*A30P)M30Sud/J 008389 C57BL/6-Tg(THY1-SNCA)1Sud/J 008474 STOCK Tg(THY1-SNCA*A53T)F53Sud/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; 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
Helpful Links
Genotyping resources and troubleshooting
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 relatedBen 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]
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]
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) 03-JAN-07 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $243.50 Female or Male Hemizygous for Tg(Prnp-SNCA*A53T)83Vle $243.50 Female or Male Homozygous for Tg(Prnp-SNCA*A53T)83Vle
Pairs /Price (US dollars $) Pair Genotype $487.00 Hemizygous for Tg(SNCA)83Vle x Hemizygous for Tg(SNCA)83Vle
Additional Supply Details
| Pricing for International shipping destinations |
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Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Hemizygous for Tg(Prnp-SNCA*A53T)83Vle $316.60 Female or Male Homozygous for Tg(Prnp-SNCA*A53T)83Vle
Pairs /Price (US dollars $) Pair Genotype $633.10 Hemizygous for Tg(SNCA)83Vle x Hemizygous for Tg(SNCA)83Vle
Additional Supply Details
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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 approximately 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 two business days following order placement. |
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| Supply Notes |
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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. | ||
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