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| These ROSA26-Syn119 mice allow cre-inducible expression of the Syn119 C-terminally truncated mutation of human alpha-synuclein (human α-Syn119 or SynCT119; associated with familial Parkinson's disease), and may be useful for studying the progressive dopaminergic neurodegeneration of Parkinson's disease and other synucleinopathies, Lewy bodies, and synaptic plasticity. | |||||||||||||||
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x Heterozygote (Female x Male) 08-AUG-09 Species laboratory mouse Generation F?+N1F1 (12-NOV-09) Donating Investigator Darren Moore, Ecole Polytechnique Federale de Lausanne Donating Investigator Ted Dawson, Johns Hopkins Univ School of Medicine Description
Homozygous ROSA26-Syn119 mice are viable and fertile, with the familial Parkinson's disease-associated Syn119 C-terminal truncation of human alpha-synuclein (human α-Syn119 or SynCT119) inserted into the Gt(ROSA)26Sor (ROSA26) locus. Widespread expression of human α-Syn119 is blocked by an upstream loxP-flanked STOP sequence (in the absence of Cre recombinase, no human α-Syn119 protein is observed in brain regions). When bred to cre expressing mice, the STOP sequence is deleted in the tissues of offspring where Cre recombinase is present; resulting in human α-Syn119 expression. In particular, Stock No. 008601 B6.Cg-Tg(Th-cre)1Tmd/J may be useful for this application. These ROSA26-Syn119 mice allow inducible expression of a human mutation associated with familial Parkinson's disease and may be useful for studying the progressive dopaminergic neurodegeneration of Parkinson's disease and other synucleinopathies, Lewy bodies, and synaptic plasticity.When bred to a strain expressing Cre recombinase in central catecholaminergic neurons (see Stock No. 008601 for example), this mutant mouse strain may be useful in studies of Parkinson's disease.
Development
A targeting vector was designed with an SV40 splice acceptor, a loxP-flanked STOP cassette (PGK-neo and triple SV40 transcriptional termination sequence), a cDNA encoding the 119 amino acid C-terminal truncation of human alpha-synuclein associated with familial Parkinson's disease (Syn119 or SynCT119; encoding amino acids 1-119 of the full length protein), and a bovine polyadenylation signal. This construct was inserted into the Gt(ROSA)26Sor locus via electroporation into into 129/SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6J mice to generate the mutant colony. ROSA26-Syn119 mice were bred to C57BL/6 for 2-3 generations and then bred together to make homozygous prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Gt(ROSA)26Sor
View Strains carrying other alleles of Gt(ROSA)26Sor (64 strains)
Introduction to Cre-lox technology
View Related Disease (OMIM) Terms
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Gt(ROSA)26Sortm2(SNCA*119)Djmo/Gt(ROSA)26Sortm2(SNCA*119)Djmo
involves: 129 * C57BL/6J (conditional)
- normal phenotype
- no abnormal phenotype detected (MGI Ref ID J:147331)
- mice are viable and fertile
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Gt(ROSA)26Sortm2(SNCA*119)Djmo/Gt(ROSA)26Sor+ Tg(Nes-cre)1Kln/0
involves: 129 * C57BL/6 * SJL (conditional)
- normal phenotype
- no abnormal phenotype detected (MGI Ref ID J:150777)
Gt(ROSA)26Sortm2(SNCA*119)Djmo/Gt(ROSA)26Sortm2(SNCA*119)Djmo Tg(Th-cre)1Tmd/0
involves: 129 * C57BL/6 (conditional)
- nervous system phenotype
- decreased dopamine level (MGI Ref ID J:150777)
- 32% reduction in levels of striatal dopamine observed in 10-11 month old mice
- homeostasis/metabolism phenotype
- abnormal serotonin level (MGI Ref ID J:150777)
- increased levels of 5-HT observed in prefrontal cortex in 10-11 month old mice
- increased circulating noradrenaline level (MGI Ref ID J:150777)
- increased levels of norepinephrine observed in striatum in 10-11 month old mice
Gt(ROSA)26Sortm2(SNCA*119)Djmo/Gt(ROSA)26Sortm2(SNCA*119)Djmo Tg(Th-cre)1Tmd/0
involves: 129 * C57BL/6 * SJL (conditional)
- homeostasis/metabolism phenotype
- abnormal serotonin level (MGI Ref ID J:150777)
- 5-HT levels are elevated in the prefrontal cortex at 10-11 months of age compared to controls
- nervous system phenotype
- abnormal neurotransmitter level (MGI Ref ID J:150777)
- norepinephrine levels in the striatum are elevated at 10-11 months of age compared to controls
- decreased dopamine level (MGI Ref ID J:150777)
- there are significant reductions in the levels of striatal dopamine (~32%), dihydroxyphenylacetic acid (~46%) and homovanillic acid (~33%) compared to controls at 10-11 months of age
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Neurobiology Research
Ataxia (Movement) Defects
Cre-lox System
loxP-flanked Sequences
Neurodegeneration
Neurotransmitter Receptor and Synaptic Vesicle Defects
Parkinson's Disease
synuclein mutants
Research Tools
Cre-lox System
loxP-flanked Sequences
Genetics Research
Mutagenesis and Transgenesis: Cre-lox System
Neurobiology Research
| Allele Symbol | Gt(ROSA)26Sortm2(SNCA*119)Djmo | ||
|---|---|---|---|
| Allele Name | Targeted mutation 2, Darren Moore | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | ROSA26-Syn119; ROSA26-SynCT119Tg; ROSA26-a-synuclein C-terminal truncation variant (Syn119); | ||
| Mutation Made By | Darren Moore, Ecole Polytechnique Federale de Lausanne | ||
| Strain of Origin | 129 | ||
| ES Cell Line Name | Other (see notes) | ||
| ES Cell Line Strain | 129 | ||
| Gene Symbol and Name | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | AV258896; Gtrgeo26; Gtrosa26; R26; ROSA26; beta geo; expressed sequence AV258896; gene trap ROSA 26; gene trap ROSA b-geo 26; | ||
| General Note | Authors state that 129/SvJ-derived embryonic stem cells were used. | ||
| Molecular Note | A targeting vector was designed with an SV40 splice acceptor, a loxP-flanked STOP cassette (PGK-neo and triple SV40 transcriptional termination sequence), a cDNA encoding the 119 amino acid C-terminal truncation of human alpha-synuclein associated with familial Parkinson's disease (Syn119 or SynCT119; encoding amino acids 1-119 of the full length protein), and a bovine polyadenylation signal. [MGI Ref ID J:147331] [MGI Ref ID J:150777] | ||
Genotyping Protocols
Gt(ROSA)26Sortm1sor STD, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
Daher JP; Ying M; Banerjee R; McDonald RS; Dumas Hahn M; Yang L; Beal MF; Thomas B; Dawson VL; Dawson TM; Moore DJ. 2009. Conditional transgenic mice expressing C-terminally truncated human alpha-synuclein (alphaSyn119) exhibit reduced striatal dopamine without loss of nigrostriatal pathway dopaminergic neurons. Mol Neurodegener 4(1):34. [PubMed: 19630976] [MGI Ref ID J:150777]
Gt(ROSA)26Sortm2(SNCA*119)Djmo relatedMoore D. 2009. Generation of a conditional knockin allele expresing a truncated human alpha-synuclein (SNCA) MGI Direct Data Submission :. [MGI Ref ID J:147331]
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred together. Mating System Heterozygote x Heterozygote (Female x Male) 08-AUG-09 Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $243.50 Female or Male Heterozygous for Gt(ROSA)26Sortm2(SNCA*119)Djmo $300.70 Female or Male Homozygous for Gt(ROSA)26Sortm2(SNCA*119)Djmo
Pairs /Price (US dollars $) Pair Genotype $487.00 Heterozygous for Gt(ROSA)26Sortm2(SNCA*119)Djmo x Heterozygous for Gt(ROSA)26Sortm2(SNCA*119)Djmo
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Heterozygous for Gt(ROSA)26Sortm2(SNCA*119)Djmo $391.00 Female or Male Homozygous for Gt(ROSA)26Sortm2(SNCA*119)Djmo
Pairs /Price (US dollars $) Pair Genotype $633.10 Heterozygous for Gt(ROSA)26Sortm2(SNCA*119)Djmo x Heterozygous for Gt(ROSA)26Sortm2(SNCA*119)Djmo
| 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 approximately 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 two business days following order placement. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| 000664 C57BL/6J | (approximate) | |
| 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. | ||
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