These double-knockout mice for alpha and beta-synucleins exhibit decreased dopamine levels and are useful in studies of synaptic function and neurodegeneration.
Dr. Thomas C. Sudhof, Stanford University School of Medicine
|Allele Type||Gene Symbol||Gene Name|
|Allele Type||Gene Symbol||Gene Name|
Mice homozygous for this targeted mutation are viable and fertile and do not display any gross physical or behavioral abnormalities. No protein product from these targeted genes is detected in brain tissue. Overall brain morphology and structure appears normal. No significant changes in the ultrastructure, short- or long-term synaptic plasticity, or in the pool size or replenishment of recycling synaptic vesicles is detected. Dopamine levels in the double targeted mice are decreased by approximately 20%, but dopamine uptake and release from isolated nerve terminals is normal. Serotonin levels are unchanged. This mutant mouse strain represents a model that may be useful in studies of synaptic function and neurodegenerative disease.
A targeting vector introducing loxP sites on either side of exon 2 (encoding residues 1-41) was used to target the Sncb gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl +-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting mice were crossed with a protamine-Cre strain to remove the floxed exon. A targeting vector containing a neomycin resistance gene was used to delete the first coding exon (residues 1-40) of the Snca gene. The construct was electroporated into 129P2/OlaHsd ?derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric mice were crossed with C57BL/6 mice. The strain has been backcrossed to C57BL/6 for several generations by the donating laboratory. Mice carrying the independent targeted mutation genes were intercrossed to generate animals with both mutations.
|Allele Name||targeted mutation 1, Thomas C Sudhof|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Snca, synuclein, alpha|
|Gene Synonym(s)||NACP; PARK1; PARK4; PD1; alpha-synuclein; alphaSYN|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||The first coding exon, encoding residues 1-40, was deleted via homologous recombination. Immunoblotting confirmed the lack of protein in mutant mice brains.|
|Allele Name||targeted mutation 1.1, Thomas C Sudhof|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||BSR; beta-|
|Gene Symbol and Name||Sncb, synuclein, beta|
|Gene Synonym(s)||AI838531; betaSYN; expressed sequence AI838531|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|Molecular Note||Sncbtm1Sud mice were crossed with mice expressing cre in the germline, thereby removing floxed exon 2, which encodes amino acids 1-41.|
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