Overview

Also Known As:Snca delta flox ("clean KO") & Rosa26-stop-lacZ

These Snca^Δflox Rosa26-stop-lacZ reporter mice carry a knock out allele of the Snca gene and the Gt(ROSA)26Sor^tm1Sho Cre reporter allele. This strain may be useful for generating mutants in which Cre recombinase efficiency can be monitored for applications related to neurodegenerative synucleinopathies, such as Parkinson's disease and multiple system atrophy.

Donating Investigator

Vladimir L Buchman, Cardiff University School of Biosciences

Genetic overview

Genetic Background	Generation

Snca^tm1.2Vlb

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

Gt(ROSA)26Sor^tm1Sho

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Reporter)	Gt(ROSA)26Sor	gene trap ROSA 26, Philippe Soriano

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Research Applications

Neurobiology Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These mice carry the Snca^Δflox allele (028559) and the Rosa26-stop-lacZ reporter allele (003504).
The "Snca^Δflox" knock-out allele contains a 1164 bp fragment deletion (including the first coding exon (exon II) and adjacent flanking sequence) of the Snca (synuclein, alpha) gene.
The Gt(ROSA)26Sor^tm1Sho allele contains a loxP-flanked DNA STOP sequence preventing expression of the downstream lacZ gene. When crossed with a cre recombinase expressing strain, the STOP sequence is removed and lacZ is expressed in cells/tissues where cre is expressed.

The Rosa26-stop-lacZ reporter allele in this double mutant line allows for the monitoring of Cre recombination efficiency when crossed to mice carrying a floxed Snca allele (see 025636).
Of note, because the Snca and Rosa26 loci are located on chromosome 6, approximately 50 Mb apart, there is a possibility that recombination can separate the mutant alleles during breeding.
Mice that are homozygous for these alleles are viable and fertile.

Mutations in human SNCA that result in aberrant polymerization and fibrillar aggregations are associated with neurodegenerative synucleinopathies, such as Parkinson's disease and multiple system atrophy.

Development

Mice carrying SncaΔflox and ROSA26-stop-lacZ reporter (Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5037-42) loci linked at the same chromosome as the result of natural crossover were selected from a pool of animals generated during crossbreeding of two mouse lines (both on C57BL/6 background), each bearing one of these modified loci.

For the Snca^tm1.2Vlb allele, a targeting vector containing a FRT site-flanked NEO cassette and a loxP site was inserted downstream of exon II (the first coding exon) of the targeted Snca gene, and another loxP site was inserted upstream of exon II. This construct was electroporated into C57BL/6N-A^tm1Brd-derived JM8A3.N1 embryonic stem (ES) cells. The resulting chimeric animals were bred to C57BL/6J mice for 2 generations and then crossed to transgenic mice (on a congenic C57BL/6 genetic background) expressing FLP recombinase under the control of the human ACTB promoter, generating Snca^floxΔneo mice. The FLP recombinase mediated excision of the FRT flanked NEO cassette and a 400 bp fragment encompassing a simple repeat region does not affect Snca locus expression. The Snca^floxΔneo mice that retained the floxed exon II were bred to C57BL/6J mice for 2 generations to remove the FLP recombinase transgene, before being intercrossed to generate homozygotes. These homozygous Snca^floxΔneo/^floxΔneo mice were then bred to transgenic mice (on the C57BL/6 background) expressing Cre recombinase under the control of the CMV promoter (see, for example, Stock No. 006054) to excise the floxed exon II and flanking sequences. The resulting knock-out Snca^Δflox mice were then bred to C57BL/6J to remove the Cre recombinase transgene and further backcrossed with C57BL/6J mice for more than 4 generations.

For the Gt(ROSA)26Sor^tm1Sho, the R26R targeting construct was created by subcloning the pROSA26-1 vector, and inserting a splice acceptor sequence (identical to the one used in the original gene trap allele), a loxP-flanked STOP sequence (containing a neo cassette and triple polyadenylation (STOP) sequence), a lacZ gene, and a polyadenylation sequence at a unique site approximately 300-bp 5' of the original gene trap integration site. Transcriptional read-through is prevented with the use of a triple polyadenylation (STOP) sequence at the 3' end of the neo expression cassette. The construct was electroporated into 129S4/SvJaeSor derived AK7 embryonic stem (ES) cells. (see, for example, Stock No. 003474)

The single mutant lines were crossed to generate double mutant animals. The mice were then bred to select for these Snca^Δflox ROSA26-stop-lacZ reporter mice carrying both mutant alleles on the same chromosome.
The mice were then bred to homozygosity for both alleles.
Upon arrival, embryos were cryopreserved.

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Two of the 27 markers throughout the genome were segregating, suggesting an incomplete backcross. One of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Expression Data

Expressed Gene	Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli
Site of Expression	when crossed to a cre recombinase-expressing strain, lacZ expression is observed in the cre-expressing tissues; this is similar to Gt(ROSA)26Sor^tm1Sor but has one copy of the loxP-flanked reporter gene

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Ninkina N; Connor-Robson N; Ustyugov AA; Tarasova TV; Shelkovnikova TA; Buchman VL. 2015. A novel resource for studying function and dysfunction of alpha-synuclein: mouse lines for modulation of endogenous Snca gene expression. Sci Rep 5:16615PubMed: 26564109 MGI: J:227400
Soriano P. 1999. Generalized lacZ expression with the ROSA26 Cre reporter strain [letter] Nat Genet 21(1):70-1PubMed: 9916792 MGI: J:64292

View All References

Genetics

Snca^tm1.2Vlb

Allele Symbol: Snca^tm1.2Vlb

Allele Name	targeted mutation 1.2, Vladimir L Buchman
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Snca^{delta floxed}
Gene Symbol and Name	Snca, synuclein, alpha
Gene Synonym(s)
Strain of Origin	C57BL/6N-A^tm1Brd
Chromosome	6
Molecular Note	A targeting vector containing a FRT site-flanked neo cassette and a loxP site was inserted downstream of exon 2 (the first coding exon) of the targeted gene, and another loxP site was inserted upstream of exon 2. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 2 floxed. Germline, Cre-mediated recombination removed exon 2. Western blot analysis of neural tissues confirmed that no protein is expressed.

Gt(ROSA)26Sor^tm1Sho

Allele Symbol: Gt(ROSA)26Sor^tm1Sho

Allele Name	targeted mutation 1, Stuart Orkin
Allele Type	Targeted (Conditional ready (e.g. floxed), Reporter)
Allele Synonym(s)	gtROSA; R26^fslz; R26-beta-gal^fl-STOP; R26R; R26Rosa-lox-Stop-lox-LacZ; R26RstoplacZ; Rosa26^fsLz; ROSA26-loxP-stoploxP-beta-geo; ROSA26R-LacZ reporter; ROSA26-stop-lacZ
Gene Symbol and Name	Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano
Gene Synonym(s)
Expressed Gene	Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli
Site of Expression	when crossed to a cre recombinase-expressing strain, lacZ expression is observed in the cre-expressing tissues; this is similar to Gt(ROSA)26Sor^tm1Sor but has one copy of the loxP-flanked reporter gene
Strain of Origin	129S4/SvJaeSor
Chromosome	6
General Note	Mice carrying this mutation are considered to be reporter strains, with successful Cre excision indicated by beta-gal expression in Cre-expressing tissues.
Molecular Note	A targeting vector was designed to insert floxed (flanked by loxP) phosphoglycerate kinase-1-cytosine deaminase/phosphoglycerate kinase-1-puromycin (PGK-CD/PGK-Puro) and stop sequences between the splicing acceptor (SA) and the beta-gal-neomycin phosphotransferase fusion gene (beta-geo) sequences of the proviral ROSA 26 locus. Correctly targeted, this resulted in ES cells that were Puro resistant but G418 susceptible, and did not express beta-gal.
Mutations Made By	Dr. Xiaohong Mao, Novartis

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Parkinson's Disease
  - synuclein mutants
Research Tools
- Neurobiology Research

Mammalian Phenotype Terms by Genotype

References

Ninkina N; Connor-Robson N; Ustyugov AA; Tarasova TV; Shelkovnikova TA; Buchman VL. 2015. A novel resource for studying function and dysfunction of alpha-synuclein: mouse lines for modulation of endogenous Snca gene expression. Sci Rep 5:16615PubMed: 26564109 MGI: J:227400
Soriano P. 1999. Generalized lacZ expression with the ROSA26 Cre reporter strain [letter] Nat Genet 21(1):70-1PubMed: 9916792 MGI: J:64292

Additional - Gt(ROSA)26Sor^tm1Sho related

Additional - Snca^tm1.2Vlb related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Snca Alternate1
- Standard PCR:Gt(ROSA)26Sor STD
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygous for both alleles. Of note, because the Snca and Rosa26 loci are located on chromosome 6, approximately 50 Mb apart, there is a possibility that recombination can separate the mutant alleles during breeding.
- Additional Breeding and Husbandry Support
Citation
When using the Snca delta flox ("clean KO") & Rosa26-stop-lacZ mouse strain in a publication, please cite the originating article(s) and include JAX stock #028560 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for Snca<tm1.2Vlb> and Gt(ROSA)26Sor<tm1Sho>, 1 pair minimum

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

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Licensing Information

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Also Known As:Snca delta flox ("clean KO") & Rosa26-stop-lacZ

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Sncatm1.2Vlb

Allele Symbol: Sncatm1.2Vlb

Gt(ROSA)26Sortm1Sho

Allele Symbol: Gt(ROSA)26Sortm1Sho

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Gt(ROSA)26Sortm1Sho related

Additional - Sncatm1.2Vlb related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

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^tm1.2Vlb

Allele Symbol: Snca^tm1.2Vlb

Gt(ROSA)26Sor^tm1Sho

Allele Symbol: Gt(ROSA)26Sor^tm1Sho

Additional - Gt(ROSA)26Sor^tm1Sho related

Additional - Snca^tm1.2Vlb related