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| These mice harbor a null mutation of the γ-synuclein gene (Sncg) and may be useful in studying synuclein function in neurodegenerative diseases, such as Parkinson's disease. | |||||||||||||||
- 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
Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N13+F1pN1
Generation DefinitionsDonating Investigator Vladimir Buchman, Cardiff University School of Biosciences Description
Mice homozygous for this γ-synuclein mutant allele are viable and fertile with no obvious abnormalities in development, behavior, or gross morphology of the nervous system. No RNA or protein expression from the targeted gene is observed. Slight upregulation of β-synuclein is reported in the midbrain of homozygous mice. Homozygous mice are also resistant to the inflammatory/apoptotic Parkinson's disease-like pathology that results following MPTP neurotoxin administration (the active form of which (MPP+) gains entry into dopaminergic cells via the dopamine transporter (DAT)). These γ-synuclein mutant mice may be useful in studying synuclein function in neurodegenerative diseases, such as Parkinson's disease.Development
A targeting vector was designed to replace exons 1-3 of the targeted gene with a PGK-neo cassette. The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and the resulting chimeric animals were bred with C57BL/6J inbred mice. Next, mutant mice were backcrossed to C57BL/6J for at least 12 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Parkinson's Disease Models
View Parkinson's Disease Models (99 strains)
012769 C57BL/6-Tg(Thy1-Sncg)HvP36Putt/J
Additional Web Information
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
assigned by genotype
Sncgtm1Vlb/Sncgtm1Vlb
B6.129P2-Sncgtm1Vlb
- nervous system phenotype
- *normal* nervous system phenotype
- homozygotes are viable, fertile and display no morphological or functional abnormalities of the nervous system relative to wild-type controls (MGI Ref ID J:86439)
- normal numbers of motoneurons in five brain stem motor nuclei, including facial, oculomotor, hypoglossal, trigeminal motor, and trochlear nuclei (MGI Ref ID J:86439)
- normal numbers of sensory neurons in trigeminal ganglia and L6 lumbar dorsal root ganglia (MGI Ref ID J:86439)
- normal morphology and numbers of myelinated A-fibers and unmyelinated C-fibers in adult saphenous nerves (MGI Ref ID J:86439)
- normal survival characteristics of P2 trigenimal ganglion neurons in various culture conditions (MGI Ref ID J:86439)
- normal sensory recovery after chronic constriction injury (CCI) to the sciatic nerve, suggesting that nerve regeneration and plasticity of early somatosensory pathways remains intact (MGI Ref ID J:86439)
- no significant differences in dopamine or its metabolite (DOPAC, 5-HIAA and HVA) levels in the striatum at 9 months of age (MGI Ref ID J:92213)
- decreased dopaminergic neuron number
- early postnatal (P5) and adult (18 months) homozygotes show a similar (15-20%) reduction in the number of tyrosine hydroxylase (TH)-positive dopaminergic neurons in substantia nigra pars compacta (SNpc) but not in ventral tegmental area (VTA) relative to wild-type controls (MGI Ref ID J:92213)
- however, no differences in the number of midbrain dopaminergic neurons are detected in SNpc at E18 (MGI Ref ID J:92213)
- also, no significant decrease in the number of TH-positive dopaminergic neurons is noted in SNpc after methyl-phenyl-tetrahydropyridine (MPTP) treatment relative to controls (MGI Ref ID J:92213)
- decreased susceptibility to dopaminergic neuron neurotoxicity
- homozygotes display resistance of SNpc dopaminergic neurons to MPTP neurotoxicity (MGI Ref ID J:92213)
- homeostasis/metabolism phenotype
- decreased susceptibility to dopaminergic neuron neurotoxicity
- homozygotes display resistance of SNpc dopaminergic neurons to MPTP neurotoxicity (MGI Ref ID J:92213)
- behavior/neurological phenotype
- *normal* behavior/neurological phenotype
- adult male homozygotes show normal behavioral reflex responses to noxious radiant heat and graded mechanical stimuli in the CCI model of neuropathic pain (MGI Ref ID J:86439)
- homozygotes are behaviorally normal and show no detectable motor dysfunction in either constant speed or accelerating rotarod tests (MGI Ref ID J:92213)
- cellular phenotype
- decreased susceptibility to dopaminergic neuron neurotoxicity
- homozygotes display resistance of SNpc dopaminergic neurons to MPTP neurotoxicity (MGI Ref ID J:92213)
This mouse can be used to support research in many areas including:
Neurobiology Research
Neurodegeneration
Parkinson's Disease
resistance to MPTP
synuclein mutants
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Sncgtm1Vlb | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Vladimir L Buchman | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | TgHSNCGtm1VLB; | ||
| Mutation Made By | Vladimir Buchman, Cardiff University School of Biosciences | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14TG2a | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Gene Symbol and Name | Sncg, synuclein, gamma | ||
| Chromosome | 14 | ||
| Gene Common Name(s) | BCSG1; C79089; EST C79089; SR; persyn; | ||
| Molecular Note | Exons 1 through 3 were replaced with a neomycin selection cassette inserted by homologous recombination. Transcript was undetected in homozygous mutant mice by Northern blot analysis of RNA obtained from various tissues. Western blot analysis of total spinal cord protein indicated an absence of protein in homozygous mutant mice. [MGI Ref ID J:86439] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Sncgtm1Vlb, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Ninkina N; Papachroni K; Robertson DC; Schmidt O; Delaney L; O'Neill F; Court F; Rosenthal A; Fleetwood-Walker SM; Davies AM; Buchman VL. 2003. Neurons expressing the highest levels of gamma-synuclein are unaffected by targeted inactivation of the gene. Mol Cell Biol 23(22):8233-45. [PubMed: 14585981] [MGI Ref ID J:86439]
Additional References
Senior SL; Ninkina N; Deacon R; Bannerman D; Buchman VL; Cragg SJ; Wade-Martins R. 2008. Increased striatal dopamine release and hyperdopaminergic-like behaviour in mice lacking both alpha-synuclein and gamma-synuclein. Eur J Neurosci 27(4):947-57. [PubMed: 18333965] [MGI Ref ID J:132938]
Sncgtm1Vlb relatedAl-Wandi A; Ninkina N; Millership S; Williamson SJ; Jones PA; Buchman VL. 2010. Absence of alpha-synuclein affects dopamine metabolism and synaptic markers in the striatum of aging mice. Neurobiol Aging 31(5):796-804. [PubMed: 19097673] [MGI Ref ID J:159589]
Anwar S; Peters O; Millership S; Ninkina N; Doig N; Connor-Robson N; Threlfell S; Kooner G; Deacon RM; Bannerman DM; Bolam JP; Chandra SS; Cragg SJ; Wade-Martins R; Buchman VL. 2011. Functional alterations to the nigrostriatal system in mice lacking all three members of the synuclein family. J Neurosci 31(20):7264-74. [PubMed: 21593311] [MGI Ref ID J:173360]
Burre J; Sharma M; Tsetsenis T; Buchman V; Etherton M; Sudhof TC. 2010. {alpha}-Synuclein Promotes SNARE-Complex Assembly in Vivo and in Vitro. Science :. [PubMed: 20798282] [MGI Ref ID J:164218]
Greten-Harrison B; Polydoro M; Morimoto-Tomita M; Diao L; Williams AM; Nie EH; Makani S; Tian N; Castillo PE; Buchman VL; Chandra SS. 2010. alphabetagamma-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction. Proc Natl Acad Sci U S A 107(45):19573-8. [PubMed: 20974939] [MGI Ref ID J:167549]
Nguyen JV; Soto I; Kim KY; Bushong EA; Oglesby E; Valiente-Soriano FJ; Yang Z; Davis CH; Bedont JL; Son JL; Wei JO; Buchman VL; Zack DJ; Vidal-Sanz M; Ellisman MH; Marsh-Armstrong N. 2011. Myelination transition zone astrocytes are constitutively phagocytic and have synuclein dependent reactivity in glaucoma. Proc Natl Acad Sci U S A 108(3):1176-81. [PubMed: 21199938] [MGI Ref ID J:168848]
Papachroni K; Ninkina N; Wanless J; Kalofoutis AT; Gnuchev NV; Buchman VL. 2005. Peripheral sensory neurons survive in the absence of alpha- and gamma-synucleins. J Mol Neurosci 25(2):157-64. [PubMed: 15784963] [MGI Ref ID J:121324]
Robertson DC; Schmidt O; Ninkina N; Jones PA; Sharkey J; Buchman VL. 2004. Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double alpha/gamma-synuclein null mutant mice. J Neurochem 89(5):1126-36. [PubMed: 15147505] [MGI Ref ID J:92213]
Senior SL; Ninkina N; Deacon R; Bannerman D; Buchman VL; Cragg SJ; Wade-Martins R. 2008. Increased striatal dopamine release and hyperdopaminergic-like behaviour in mice lacking both alpha-synuclein and gamma-synuclein. Eur J Neurosci 27(4):947-57. [PubMed: 18333965] [MGI Ref ID J:132938]
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 maintaining a live colony, homozygous mice may be bred.
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 | ||
| 000664 C57BL/6J | ||
| 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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