Homozygous null mice suffer from a reduction in total striatal dopamine and exhibit an attenuated locomotor response when given amphetamine. Observed phenotype suggests that Snca is an activity-dependent negative regulator of dopamine neurotransmission. These mice may be useful in studies relating to Parkinson's disease.
Dr. Arnon Rosenthal, Rinat Neuroscience Corporation
Homozygous null mice are viable, fertile, normal in size and do not display any gross abnormalities. No gene product (mRNA or protein) is detected in brain tissue. A wild-type complement of dopamine neurons, fibers and synaptic terminals is present and the overall brain architecture appears to be intact. They suffer from a reduction in total striatal dopamine and exhibit an attenuated locomotor response when given amphetamine. Normal dopamine release is observed upon stimulation of the nigrostriatal terminal with a single electrical pulse. When multiple stimuli are applied however, null mice exhibit an accelerated recovery of dopamine release. A similar acceleration is seen in wildtype mice in the presence of increased extracellular calcium. The phenotype observed in homozygous Snca-null mice suggests that Snca is an activity-dependent negative regulator of dopamine neurotransmission.
A targeting vector containing a neomycin resistance gene driven by a phosphoglycerate 1 promoter was used to disrupt Snca exons 1-2 in RW-4 embryonic stem (ES) cells. These two exons encode amino acids 1-41. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric animals were obtained.
|Allele Name||targeted mutation 1, Arnon Rosenthal|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||alpha-Syn-; alpha-Synko|
|Gene Symbol and Name||Snca, synuclein, alpha|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A PGK-neo cassette was used to delete exons 1 and 2, encoding amino acids 1 through 41 as well as a 5' untranslated region. RT-PCR analysis of extracts from the brains of homozygous mutant mice, using probes for both the deleted 5' region as well the untargeted 3' region, showed an absence of transcript. Western blot analysis, immunohistochemical analysis, and in situ hybridization confirmed a lack of encoded protein in homozygous mutant mice.|
This strain arose on a B6;129X background. It is maintained on a B6;129X background. Coat color expected from breeding:Black or Agouti
When using the α-Syn- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003692 in your Materials and Methods section.