Overview

Also Known As:SNCA-OVX

This strain is currently unavailable due to replenishing of cryopreserved stocks.

These SNCA-OVX mice express a transgene containing the human SNCA gene and develop age-dependent motor incoordination and loss of nigrostriatal dopamine neurons. They are suitable for use in applications related to the study of Parkinson disease.

Donating Investigator

Richard Wade-Martins, University of Oxford

Genetic overview

Genetic Background	Generation

Snca^tm1Rosl

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Snca	synuclein, alpha

Tg(SNCA)OVX37Rwm

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

View Genetics

Research Applications

Neurobiology Research
Research Tools

View All Research Applications

Details

Detailed Description

These mutant mice carry a transgene containing human SNCA gene and a knock out allele of the mouse Snca gene. Human α-synuclein protein levels in the striatum of mutant mice is 1.9-fold higher than levels of endogenous mouse α-synuclein protein. Transgene expression is detected in the striatum (caudate putamen and nucleus accumbens). Mice that are homozygous for the targeted mutation and the transgene are viable and fertile. Male mice have an increased dry stool weight. SNCA-OVX mice, aged 18 months, exhibit age-related impairment of motor coordination, and loss of nigrostriatal dopamine neurons. Diminishment of motor coordination and firing rate of dopamine neurons of the substantia nigra pars compacta is age-dependent. Dopamine transmission in the dorsal striatum is reduced as early as 3-4 months of age. The transgene was detected at a single site of integration near the centromere of chromosome 4 by fluorescence in situ hybridization analysis.

Development

A BAC construct carrying the complete 111-kb human wildtype SNCA locus and endogenous promoter sequences was microinjected into the pronucleus of CBA X C57BL/6 F1 fertilized eggs. Founder line 37 was subsequently crossed to mice carrying the Snca^tm1Rosl allele (see, for example, Stock No. 003692) on a congenic C57BL/6 background for 9 generations. The transgene was detected at a single site of integration near the centromere of chromosome 4 by fluorescence in situ hybridization analysis. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Expression Data

Expressed Gene	SNCA, synuclein alpha, human
Site of Expression	Transgene expression is detected in the striatum (caudate putamen and nucleus accumbens).

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Janezic S; Threlfell S; Dodson PD; Dowie MJ; Taylor TN; Potgieter D; Parkkinen L; Senior SL; Anwar S; Ryan B; Deltheil T; Kosillo P; Cioroch M; Wagner K; Ansorge O; Bannerman DM; Bolam JP; Magill PJ; Cragg SJ; Wade-Martins R. 2013. Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model. Proc Natl Acad Sci U S A 110(42):E4016-25PubMed: 24082145 MGI: J:201991

View All References

Genetics

Snca^tm1Rosl

Allele Symbol: Snca^tm1Rosl

Allele Name	targeted mutation 1, Arnon Rosenthal
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	alpha-Syn^-; alpha-Synko
Gene Symbol and Name	Snca, synuclein, alpha
Gene Synonym(s)
Strain of Origin	129X1/SvJ
Chromosome	6
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.

Tg(SNCA)OVX37Rwm

Allele Symbol: Tg(SNCA)OVX37Rwm

Allele Name	transgene insertion OVX37, Richard Wade-Martins
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	SNCA-OVX
Gene Symbol and Name	Tg(SNCA)OVX37Rwm, transgene insertion OVX37, Richard Wade-Martins
Gene Synonym(s)
Promoter	SNCA, synuclein alpha, human
Expressed Gene	SNCA, synuclein alpha, human
Site of Expression	Transgene expression is detected in the striatum (caudate putamen and nucleus accumbens).
Strain of Origin	(CBA x C57BL/6)F1
Chromosome	4
Molecular Note	This transgene consists of a BAC carrying the complete 111-kb wild-type human SNCA locus. This line overexpresses the human protein at nearly twice the endogenous level of the mouse protein. Fluorescence in situ hybridization analysis identified a single site of integration near the centromere of chromosome 4.

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Parkinson's disease 1

Research Areas By Phenotype

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

Neurobiology Research
- Neurodegeneration
- Ataxia (Movement) Defects
- Parkinson's Disease
  - synuclein mutants
Research Tools
- Neurobiology Research

Genotype: Snca^tm1Rosl related

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

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Snca^tm1Rosl/Snca^tm1Rosl Tg(SNCA)OVX37Rwm/0
B6.Cg-Tg(SNCA)OVX37Rwm Snca

behavior/neurological phenotype

impaired coordination
- 18 month old mutants show a reduced latency to fall on the rotarod test and are impaired on the multiple static rods test
- Normal - however, no differences in the latency to fall in the inverted screen test is seen

short stride length
- reduction in forepaw stride length in 18 month old mutants

digestive/alimentary phenotype

constipation
- dry stool weight is increased in males but not females, independent of age; however, stool frequency and stool water content are normal, indicating constipation-like phenotype

homeostasis/metabolism phenotype

increased dopamine level
- net dopamine content is unchanged in caudate putamen or nucleus accumbens at 3-4 and 12 months of age, however at 18 months of age, dopamine content is greater in the caudate putamen

nervous system phenotype

abnormal dopaminergic neuron morphology
- vesicles in dopamine axons of the dorsal striatum are more clustered than in controls at 3 months of age; the frequency distribution of intervesicle distance is reduced and vesicles are 3 times less dispersed

abnormal neuron physiology
- substantia nigra pars compacta dopamine neurons exhibit age-dependent reductions (almost 30%) in firing rates in vivo

abnormal synaptic dopamine release
- Normal - dopamine uptake kinetics are normal and norepinephrine and 5-hydroxytryptamine axonal release are normal
- efore the loss of dopamine neurons and persists throughout their lifespan
- greatest deficits in dopamine release are seen in the dorsal and lateral striatum
- in the dorsal striatum, mean peak extracellular concentrations of dopamine evoked by single electrical pulses across distributed recording sites are on average about 30% lower than in controls; this reduced release is seen from a young age of 3-4 months before the loss of dopamine neurons and persists throughout their lifespan
- the dopamine release deficit persists in the presence of nicotinic receptor blockade by dihydro-beta-erythroidine

loss of dopaminergic neurons
- 18 month old mutants exhibit loss of substantia nigra pars compacta dopamine neurons

neuron degeneration
- 18 month old mutants exhibit loss of substantia nigra pars compacta dopamine neurons
- Normal - however, aggregation of alpha-synuclein is not seen in the substantia nigra pars compacta or striatum

References

Janezic S; Threlfell S; Dodson PD; Dowie MJ; Taylor TN; Potgieter D; Parkkinen L; Senior SL; Anwar S; Ryan B; Deltheil T; Kosillo P; Cioroch M; Wagner K; Ansorge O; Bannerman DM; Bolam JP; Magill PJ; Cragg SJ; Wade-Martins R. 2013. Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model. Proc Natl Acad Sci U S A 110(42):E4016-25PubMed: 24082145 MGI: J:201991

Additional - Snca^tm1Rosl related

Additional - Tg(SNCA)OVX37Rwm related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- QPCR:Tg(SNCAcDNA)-qPCR
- Standard PCR:Tg(SNCA)129Mjff
- Standard PCR:Sncaalternate5
- Standard PCR:Tg(SNCA)
- Probe:Snca-Probe
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes for the targeted mutation and the transgene.
- Additional Breeding and Husbandry Support
Citation
When using the SNCA-OVX mouse strain in a publication, please cite the originating article(s) and include JAX stock #023837 in your Materials and Methods section.

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Also Known As:SNCA-OVX

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Sncatm1Rosl

Allele Symbol: Sncatm1Rosl

Tg(SNCA)OVX37Rwm

Allele Symbol: Tg(SNCA)OVX37Rwm

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Phenotype

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

Genotype: Sncatm1Rosl related

Mammalian Phenotype Terms by Genotype

Genotype: Sncatm1Rosl/Sncatm1Rosl Tg(SNCA)OVX37Rwm/0B6.Cg-Tg(SNCA)OVX37Rwm Snca

behavior/neurological phenotype

digestive/alimentary phenotype

homeostasis/metabolism phenotype

nervous system phenotype

References

Additional - Sncatm1Rosl related

Additional - Tg(SNCA)OVX37Rwm related

Genotyping Protocols

Breeding Considerations

Citation

Strain Interest Registration

Contact Information

Interest

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Snca^tm1Rosl

Allele Symbol: Snca^tm1Rosl

Genotype: Snca^tm1Rosl related

Genotype: Snca^tm1Rosl/Snca^tm1Rosl Tg(SNCA)OVX37Rwm/0
B6.Cg-Tg(SNCA)OVX37Rwm Snca

Additional - Snca^tm1Rosl related