B6;129-Gt(ROSA)26Sor^{tm2(SNCA*119)Djmo}/TmdJ

Stock number: 008889
Research areas: Neurobiology Research, Research Tools

Description

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.

Detailed 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.

Allele

Symbol: Gt(ROSA)26Sor^{tm2(SNCA*119)Djmo}
Name: Targeted mutation 2, Darren Moore
MGI accession ID: MGI:3840596
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence; Humanized sequence
Synonyms: ROSA26-a-synuclein C-terminal truncation variant (Syn119); ROSA26-Syn119; ROSA26-SynCT119^Tg
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Marker synonyms: beta geo; Gtrgeo26; Gtrosa26; R26; ROSA26; SETD5-AS1; Thumpd3as1
Chromosome: 6
Strain of origin: 129
Expressed genes: SNCA,synuclein alpha,human
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.
General note: The original refernece states that 129/SvJ-derived embryonic stem cells were used.