Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation [F8p]+F4 (21-NOV-07)   Donating Investigator Arnon Rosenthal,   Rinat Neuroscience Corporation

Description
Homozygous null mice are viable, fertile, normal in size and do not display any gross abnormalities. No gene product (mRNA or protein) is detected in brain tissue. A wild-type complement of dopamine neurons, fibers and synaptic terminals is present and the overall brain architecture appears to be intact. They suffer from a reduction in total striatal dopamine and exhibit an attenuated locomotor response when given amphetamine. Normal dopamine release is observed upon stimulation of the nigrostriatal terminal with a single electrical pulse. When multiple stimuli are applied however, null mice exhibit an accelerated recovery of dopamine release. A similar acceleration is seen in wildtype mice in the presence of increased extracellular calcium. The phenotype observed in homozygous Snca-null mice suggests that Snca is an activity-dependent negative regulator of dopamine neurotransmission.

Development
A targeting vector containing a neomycin resistance gene driven by a phosphoglycerate 1 promoter was used to disrupt Snca exons 1-2 in RW-4 embryonic stem (ES) cells. These two exons encode amino acids 1-41. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric animals were obtained.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Snca

006390	B6;129-Sncatm1Sud Sncbtm1.1Sud/J
008132	STOCK Tg(THY1-Snca)M1mSud/J

View Strains carrying other alleles of Snca     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Parkinson Disease, Familial, Type 1; PARK1 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
	Parkinson Disease; PD - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Snca^tm1Rosl/Snca^tm1Rosl

        involves: 129X1/SvJ * C57BL/6

• nervous system phenotype
• abnormal dopaminergic neuron morphology (MGI Ref ID J:60151)
  • when exposed to paired electrical stimuli, striatal brain slices (containing dopamine terminals) from homozygous mice exhibit a faster dopamine release recovery as compared to wild-type
  • dopamine discharge and reuptake in response to a single electrical pulse or a train of pulses is comparable to wild-type
• decreased dopamine level (MGI Ref ID J:60151)
  • dopamine content is reduced by 18% in the striatum, however, dopamine content in the ventral midbrain and nucleus accumbens is similar to wild-type
• behavior/neurological phenotype
• abnormal locomotor activation (MGI Ref ID J:60151)
  • homozygous mice exhibit an attenuated locomotor response after administration of amphetamine as compared to wild-type
  • in the absence of amphetamine, locomotor activity in the open field test is comparable to wild-type

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Snca^tm1Rosl/Snca^tm1Rosl

        involves: 129X1/SvJ

• immune system phenotype
• decreased susceptibility to bacterial infection (MGI Ref ID J:138194)
  • mice do not exhibit as much dopamine neuron loss following injection of LPS into the substantia nigra as similarly treated wild-type mice

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Parkinson's Disease (resistance to MPTP)
Parkinson's Disease (synuclein mutants)

Snca related

Neurobiology Research
Parkinson's Disease

Snca^tm1Rosl related

Neurobiology Research
Astrocyte Defects
Behavioral and Learning Defects
Neurodegeneration
Neurotransmitter Receptor and Synaptic Vesicle Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Sncatm1Rosl
Allele Name		targeted mutation 1, Arnon Rosenthal
Allele Type		Targeted (knock-out)
Common Name(s)		alpha-Syn-; alpha-Synko;
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Snca, synuclein, alpha
Chromosome		6
Gene Common Name(s)		MGC105443; MGC110988; NACP; PARK1; PARK4; PD1; alpha-synuclein; alphaSYN;
Molecular Note		A PGK-neo cassette was used to delete exons 1 and 2, encoding amino acids 1 through 41 as well as a 5' untranslated region. RT-PCR analysis of extracts from the brains of homozygous mutant mice, using probes for both the deleted 5' region as well the untargeted 3' region, showed an absence of transcript. Western blot analysis, immunohistochemical analysis, and in situ hybridization confirmed a lack of encoded protein in homozygous mutant mice. [MGI Ref ID J:60151]

Genotyping

Genotyping Information

Genotyping Protocols

Snca^tm1Rosl, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Abeliovich A; Schmitz Y; Farinas I; Choi-Lundberg D; Ho WH; Castillo PE; Shinsky N; Verdugo JM; Armanini M; Ryan A; Hynes M; Phillips H; Sulzer D; Rosenthal A. 2000. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25(1):239-52. [PubMed: 10707987]  [MGI Ref ID J:60151]

Additional References

Snca^tm1Rosl related

Alvarez-Fischer D; Henze C; Strenzke C; Westrich J; Ferger B; Hoglinger GU; Oertel WH; Hartmann A. 2008. Characterization of the striatal 6-OHDA model of Parkinson's disease in wild type and alpha-synuclein-deleted mice. Exp Neurol 210(1):182-93. [PubMed: 18053987]  [MGI Ref ID J:134020]

Duka T; Rusnak M; Drolet RE; Duka V; Wersinger C; Goudreau JL; Sidhu A. 2006. Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. FASEB J 20(13):2302-12. [PubMed: 17077307]  [MGI Ref ID J:129746]

Ebadi M; Sharma S. 2006. Metallothioneins 1 and 2 attenuate peroxynitrite-induced oxidative stress in Parkinson disease. Exp Biol Med (Maywood) 231(9):1576-83. [PubMed: 17018883]  [MGI Ref ID J:129277]

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]

Klivenyi P; Siwek D; Gardian G; Yang L; Starkov A; Cleren C; Ferrante RJ; Kowall NW; Abeliovich A; Beal MF. 2006. Mice lacking alpha-synuclein are resistant to mitochondrial toxins. Neurobiol Dis 21(3):541-8. [PubMed: 16298531]  [MGI Ref ID J:106226]

Martin ED; Gonzalez-Garcia C; Milan M; Farinas I; Cena V. 2004. Stressor-related impairment of synaptic transmission in hippocampal slices from alpha-synuclein knockout mice. Eur J Neurosci 20(11):3085-91. [PubMed: 15579163]  [MGI Ref ID J:101275]

Martin-Clemente B; Alvarez-Castelao B; Mayo I; Sierra AB; Diaz V; Milan M; Farinas I; Gomez-Isla T; Ferrer I; Castano JG. 2004. alpha-Synuclein expression levels do not significantly affect proteasome function and expression in mice and stably transfected PC12 cell lines. J Biol Chem 279(51):52984-90. [PubMed: 15466467]  [MGI Ref ID J:118517]

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]

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]

Sharon R; Bar-Joseph I; Mirick GE; Serhan CN; Selkoe DJ. 2003. Altered fatty acid composition of dopaminergic neurons expressing alpha-synuclein and human brains with alpha-synucleinopathies. J Biol Chem 278(50):49874-81. [PubMed: 14507911]  [MGI Ref ID J:118570]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	This strain arose on a B6;129X background. It is maintained on a B6;129X background. Coat color expected from breeding:Black or Agouti
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

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

Usually shipped between four and eight weeks of age. 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
	None Available
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.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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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.”

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.

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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.