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| These PAC-Tg(SNCAWT);Snca-/- mice harbor a Snca knockout allele and a transgene encoding the human α-synuclein. PAC-Tg(SNCAWT);Snca-/- mice are the experimental control for strains that model the very early gastrointestinal dysfunction in the absence of major central nervous system pathology seen in human Parkinson's disease (Stock No. 010788 and Stock No. 010799). | ||||||||||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Stock; Targeted Mutation; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System See Colony Maintenance under the Health & husbandry tab (Female x Male) 14-OCT-11 Species laboratory mouse Generation F?+ (09-MAY-11)
Generation DefinitionsDonating Investigator Robert Nussbaum, University of California San Francisco Description
These PAC-Tg(SNCAWT);Snca-/- mice are viable and fertile, harboring a Snca knockout allele and a transgene encoding the human α-synuclein. As homozygotes, expression of endogenous mouse α-synuclein is abolished and replaced by human α-synuclein from the two total insertions of the PAC-Tg(SNCAWT). While brain RNA expression of SNCAWT is more than 50-fold greater compared to normal endogenous mouse α-synuclein, protein levels are only 1 to 1.5-fold greater. In colon however, both RNA and protein expression of SNCAWT are ~100-fold greater than normal endogenous mouse α-synuclein. PAC-Tg(SNCAWT);Snca-/- mice do not show any enteric nervous system abnormalities or widespread α-synuclein aggregation in brain or colon. No detectable motor behavior impairments, autonomic abnormalities, olfactory dysfunction, dopaminergic deficits, Lewy body inclusions or neurodegeneration are associated with α-synuclein expression in these mice.These PAC-Tg(SNCAWT);Snca-/- mice are the experimental control for strains that model the very early gastrointestinal dysfunction in the absence of major central nervous system pathology seen in human Parkinson's disease (Stock No. 010788 and Stock No. 010799).
Development
To generate the PAC-Tg(SNCAWT) transgene, the 146 kb RPCI-1 human male P1 artificial chromosome (PAC) clone 27M07, containing the entire human SNCA (synuclein, alpha (non A4 component of amyloid precursor)) gene and 34 kb of its upstream region, was used. This transgene was microinjected into the pronuclei of fertilized FVB/N ova. The only transgenic founder shown to contain the complete SNCA gene was bred to FVB/N wildtype mice. These PAC-Tg(SNCAWT) transgenic mice were maintained as coisogenic on the FVB/N genetic background by breeding together as homozygotes.To generate the Snca knockout allele, a targeting vector was designed to replace exons 4 and 5 with a reverse-oriented neomycin resistance cassette (PGK-neo from the vector pPNT). The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and the resulting mutant mice were generated and maintained as coisogenic on the 129S6/SvEvTac genetic background.
To generate the PAC-Tg(SNCAWT);Snca-/- strain, mice homozygous for the PAC-Tg(SNCAWT) transgene (FVB/N genetic background) were bred with mice homozygous for the Snca knockout allele (129S6/SvEvTac genetic background). Double mutant mice were maintained on a mixed FVB/N;129S6/SvEvTac background using multiple breeding units without repeated brother-sister matings: thus the only portions of the FVB/N or 129S6/SvEvTac genomes fixed in these mice are the FVB/N regions flanking the PAC-Tg(SNCAWT) transgene insertion sites and the 129S6/SvEvTac regions around the Snca knockout allele. These PAC-Tg(SNCAWT);Snca-/- mice were sent to The Jackson Laboratory Repository. Upon arrival, mice were bred together to establish the colony.
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| Considerations for Choosing Controls | ||
Related Strains
Parkinson's Disease Models
View Parkinson's Disease Models (99 strains)
010788 FVB;129S6-Sncatm1Nbm Tg(SNCA*A30P)1Nbm Tg(SNCA*A30P)2Nbm/J 010799 FVB;129S6-Sncatm1Nbm Tg(SNCA*A53T)1Nbm Tg(SNCA*A53T)2Nbm/J
Additional Web Information
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
This mouse can be used to support research in many areas including:
Internal/Organ Research
Gastrointestinal Defects
Neurobiology Research
Ataxia (Movement) Defects
Neuromuscular Defects
Parkinson's Disease
synuclein mutants
Research Tools
Neurobiology Research
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Sncatm1Nbm | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Robert L Nussbaum | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Scna-; Snca-; | ||
| Strain of Origin | 129S6/SvEvTac | ||
| Gene Symbol and Name | Snca, synuclein, alpha | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | NACP; PARK1; PARK4; PD1; alpha-synuclein; alphaSYN; | ||
| Molecular Note | Exons 4 and 5 were replaced with a neomycin selection cassette inserted by homologous recombination. While the separation of Western blot results by 2D-PAGE showed various isoforms in total brain extract obtained from wild-type mice, protein was undetected in samples obtained from homozygous mutant mice. [MGI Ref ID J:79784] | ||
| Allele Symbol | Tg(SNCA)1Nbm | ||
| Allele Name | transgene insertion 1, Robert L Nussbaum | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | PAC-Tg(SCNAWT); | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | SNCA, synuclein, alpha (non A4 component of amyloid precursor), human | ||
| Promoter | SNCA, synuclein, alpha (non A4 component of amyloid precursor), human | ||
| Molecular Note | To generate the PAC-Tg(SNCAWT) transgene, the 146 kb RPCI-1 human male P1 artificial chromosome (PAC) clone 27M07, containing the entire human SNCA (synuclein, alpha (non A4 component of amyloid precursor)) gene and 34 kb of its upstream region, was used. This transgene was microinjected into the pronuclei of fertilized FVB/N ova. The only transgenic founder shown to contain the complete SNCA gene was bred to FVB/N wildtype mice. [MGI Ref ID J:154970] [MGI Ref ID J:86222] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(SNCA), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Cabin DE; Shimazu K; Murphy D; Cole NB; Gottschalk W; McIlwain KL; Orrison B; Chen A; Ellis CE; Paylor R; Lu B; Nussbaum RL. 2002. Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci 22(20):8797-807. [PubMed: 12388586] [MGI Ref ID J:79784]
Gispert S; Del Turco D; Garrett L; Chen A; Bernard DJ; Hamm-Clement J; Korf HW; Deller T; Braak H; Auburger G; Nussbaum RL. 2003. Transgenic mice expressing mutant A53T human alpha-synuclein show neuronal dysfunction in the absence of aggregate formation. Mol Cell Neurosci 24(2):419-29. [PubMed: 14572463] [MGI Ref ID J:86222]
Additional References
Sncatm1Nbm relatedTg(SNCA)1Nbm relatedAustin SA; Floden AM; Murphy EJ; Combs CK. 2006. Alpha-synuclein expression modulates microglial activation phenotype. J Neurosci 26(41):10558-63. [PubMed: 17035541] [MGI Ref ID J:113229]
Barcelo-Coblijn G; Golovko MY; Weinhofer I; Berger J; Murphy EJ. 2007. Brain neutral lipids mass is increased in alpha-synuclein gene-ablated mice. J Neurochem 101(1):132-41. [PubMed: 17250686] [MGI Ref ID J:122525]
Cabin DE; Gispert-Sanchez S; Murphy D; Auburger G; Myers RR; Nussbaum RL. 2005. Exacerbated synucleinopathy in mice expressing A53T SNCA on a Snca null background. Neurobiol Aging 26(1):25-35. [PubMed: 15585343] [MGI Ref ID J:124976]
Ekstrand MI; Terzioglu M; Galter D; Zhu S; Hofstetter C; Lindqvist E; Thams S; Bergstrand A; Hansson FS; Trifunovic A; Hoffer B; Cullheim S; Mohammed AH; Olson L; Larsson NG. 2007. Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons. Proc Natl Acad Sci U S A 104(4):1325-30. [PubMed: 17227870] [MGI Ref ID J:119515]
Ellis CE; Murphy EJ; Mitchell DC; Golovko MY; Scaglia F; Barcelo-Coblijn GC; Nussbaum RL. 2005. Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein. Mol Cell Biol 25(22):10190-201. [PubMed: 16260631] [MGI Ref ID J:102361]
Golovko MY; Faergeman NJ; Cole NB; Castagnet PI; Nussbaum RL; Murphy EJ. 2005. Alpha-synuclein gene deletion decreases brain palmitate uptake and alters the palmitate metabolism in the absence of alpha-synuclein palmitate binding. Biochemistry 44(23):8251-9. [PubMed: 15938614] [MGI Ref ID J:99690]
Golovko MY; Rosenberger TA; Faergeman NJ; Feddersen S; Cole NB; Pribill I; Berger J; Nussbaum RL; Murphy EJ. 2006. Acyl-CoA synthetase activity links wild-type but not mutant alpha-synuclein to brain arachidonate metabolism. Biochemistry 45(22):6956-66. [PubMed: 16734431] [MGI Ref ID J:109641]
Kuo YM; Li Z; Jiao Y; Gaborit N; Pani AK; Orrison BM; Bruneau BG; Giasson BI; Smeyne RJ; Gershon MD; Nussbaum RL. 2010. Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated {alpha}-synuclein gene mutations precede central nervous system changes. Hum Mol Genet :. [PubMed: 20106867] [MGI Ref ID J:156741]
Kurz A; Double KL; Lastres-Becker I; Tozzi A; Tantucci M; Bockhart V; Bonin M; Garcia-Arencibia M; Nuber S; Schlaudraff F; Liss B; Fernandez-Ruiz J; Gerlach M; Wullner U; Luddens H; Calabresi P; Auburger G; Gispert S. 2010. A53T-alpha-synuclein overexpression impairs dopamine signaling and striatal synaptic plasticity in old mice. PLoS One 5(7):e11464. [PubMed: 20628651] [MGI Ref ID J:163115]
Kurz A; Wohr M; Walter M; Bonin M; Auburger G; Gispert S; Schwarting RK. 2010. Alpha-synuclein deficiency affects brain Foxp1 expression and ultrasonic vocalization. Neuroscience 166(3):785-95. [PubMed: 20056137] [MGI Ref ID J:159729]
Steidinger TU; Standaert DG; Yacoubian TA. 2011. A neuroprotective role for angiogenin in models of Parkinson's disease. J Neurochem 116(3):334-41. [PubMed: 21091473] [MGI Ref ID J:170263]
Watson JB; Hatami A; David H; Masliah E; Roberts K; Evans CE; Levine MS. 2009. Alterations in corticostriatal synaptic plasticity in mice overexpressing human alpha-synuclein. Neuroscience 159(2):501-13. [PubMed: 19361478] [MGI Ref ID J:148932]
Westerlund M; Ran C; Borgkvist A; Sterky FH; Lindqvist E; Lundstromer K; Pernold K; Brene S; Kallunki P; Fisone G; Olson L; Galter D. 2008. Lrrk2 and alpha-synuclein are co-regulated in rodent striatum. Mol Cell Neurosci 39(4):586-91. [PubMed: 18790059] [MGI Ref ID J:142519]
Kuo YM; Li Z; Jiao Y; Gaborit N; Pani AK; Orrison BM; Bruneau BG; Giasson BI; Smeyne RJ; Gershon MD; Nussbaum RL. 2010. Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated {alpha}-synuclein gene mutations precede central nervous system changes. Hum Mol Genet :. [PubMed: 20106867] [MGI Ref ID J:156741]
Nussbaum RL. 2009. Generation of an SCNA (wild-type) transgene MGI Direct Data Submission :. [MGI Ref ID J:154970]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, mice homozygous for the Snca targeted mutation and homozygous for the Tg(SNCAWT) transgene are bred together. These mice are the experimental control strain for Stock No. 010788 and Stock No. 010799. Mating System See Colony Maintenance under the Health & husbandry tab (Female x Male) 14-OCT-11
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 $172.00 Female or Male Homozygous for Sncatm1Nbm, Homozygous for Tg(SNCA)1Nbm
Pairs /Price (US dollars $) Pair Genotype $344.00 Homozygous for Sncatm1Nbm, Homozygous for Tg(SNCA)1Nbm x Homozygous for Sncatm1Nbm, Homozygous for Tg(SNCA)1Nbm 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 $223.60 Female or Male Homozygous for Sncatm1Nbm, Homozygous for Tg(SNCA)1Nbm
Pairs /Price (US dollars $) Pair Genotype $447.20 Homozygous for Sncatm1Nbm, Homozygous for Tg(SNCA)1Nbm x Homozygous for Sncatm1Nbm, Homozygous for Tg(SNCA)1Nbm 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.
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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