B6;129-Gt(ROSA)26Sor^{tm3(SNCA*E46K)Djmo}/TmdJ

Stock number: 008886
Research areas: Neurobiology Research, Research Tools

Description

These ROSA26-Syn-E46K mice allow cre-inducible expression of the E46K missense mutant form of human alpha-synuclein (human E46K α-Syn or SYNE46K) associated with familial Parkinson's disease, dementia, and visual hallucinations, 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-Syn-E46K mice are viable and fertile, with the E46K missense mutant form of human alpha-synuclein (human E46K α-Syn or SYNE46K; associated with familial Parkinson's disease, dementia, and visual hallucinations) inserted into the Gt(ROSA)26Sor (ROSA26) locus. Widespread expression of human E46K α-Syn is blocked by an upstream loxP-flanked STOP sequence (in the absence of Cre recombinase, no human E46K α-Syn 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 E46K α-Syn expression. In particular, Stock No. 008601 B6.Cg-Tg(Th-cre)1Tmd/J may be useful for this application. These ROSA26-Syn-E46K mice allow inducible expression of a human mutation associated with familial Parkinson's disease, dementia, and visual hallucinations and may be useful for studying the progressive dopaminergic neurodegeneration of Parkinson's disease and other synucleinopathies, Lewy bodies, and synaptic plasticity.

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 human alpha-synuclein cDNA bearing a familial Parkinson's disease-linked E46K missense mutation (SYNE46K), 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-Syn-E46K 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^{tm3(SNCA*E46K)Djmo}
Name: Targeted mutation 3, Darren Moore
MGI accession ID: MGI:3840600
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence; Humanized sequence; No functional change
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
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 human alpha-synuclein cDNA bearing a familial Parkinson's disease-linked E46K missense mutation (SYNE46K), and a bovine polyadenylation signal.
General note: The original reference states that 129/SvJ-derived embryonic stem cells were used.