Research Models

α-synuclein KO Mouse (Conditional)

Synonyms: Sncaflox(neo), SNCAflox delta neo, Snca conditional knockout, SNCA KO Mouse (Buchman), Alpha-synuclein KO Mouse (Conditional)

Species: Mouse
Genes: SNCA
Modification: SNCA: Conditional Knock-out
Disease Relevance: Parkinson's Disease
Strain Name: B6(Cg)-Sncatm1.1Vlb/J
Genetic Background: C57BL/6J
Availability: Available through The Jackson Laboratory, Stock #025636, Live.

Summary

Breeding these mice with various Cre-expressing transgenic mice allows for the depletion of α-synuclein in specific cell populations (Ninkina et al., 2015).

For example, these mice were bred to an “early deletor” line that expresses Cre recombinase embryonically using the CMV promoter. The resulting offspring had germline deletion of the floxed exon 2. Homozygous SNCAΔfloxΔflox mice had no detectable α-synuclein protein in neuronal tissues.

The gene-targeting approach used to create these mice left behind minimal ectopic sequence, just a single loxP site.

The deletion involves a 1,164 base pair fragment consisting of exon 2 and the adjacent intronic sequences of the mouse Snca gene. Mouse lines carrying the modified Snca locus along with a Rosa26-stop-lacZ reporter cassette located in cis on chromosome 6 also have been developed (Roman et al., 2017). The reporter allows quick identification of cells with Snca inactivation.

Modification Details

A targeting vector containing a FRT site-flanked neomysin cassette and a loxP site was inserted downstream of exon 2 (the first coding exon of Snca) and another loxP site was inserted upstream of exon 2. Flp-mediated recombination removed the FRT-flanked neo cassette, leaving exon 2 floxed. When bred to Cre-expressing mice, the resulting offspring have the first coding exon deleted in Cre-expressing tissues.

Related Strains

B6(Cg)-Sncatm1.2Vlb/J - These SncaΔflox knock-out mice similarly lack the first coding exon (exon II) of the Snca gene. Available through The Jackson Laboratory Stock# 028560.

B6.Cg-Sncatm1.1Vlb Gt(ROSA)26Sortm1Sho/J - This double mutant line carries the floxed Snca 1.1 allelle (from Stock# 025636) and the ROSA26-stop-lacZ reporter allele (from Stock #003474). The ROSA26-stop-lacZ reporter allele allows for the monitoring of Cre recombinase activity.

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

No Data

  • Dopamine Deficiency
  • Non-Motor Impairment
  • α-synuclein Inclusions
  • Neuroinflammation
  • Motor Impairment
  • Mitochondrial Abnormalities
  • Neuronal Loss

Neuronal Loss

No data.

Dopamine Deficiency

No data.

α-synuclein Inclusions

No data.

Neuroinflammation

No data.

Mitochondrial Abnormalities

No data.

Motor Impairment

No data.

Non-Motor Impairment

No data.

Last Updated: 07 Feb 2019

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References

Paper Citations

  1. . A novel resource for studying function and dysfunction of α-synuclein: mouse lines for modulation of endogenous Snca gene expression. Sci Rep. 2015 Nov 13;5:16615. PubMed.
  2. . Generation of mouse lines with conditionally or constitutively inactivated Snca gene and Rosa26-stop-lacZ reporter located in cis on the mouse chromosome 6. Transgenic Res. 2017 Apr;26(2):301-307. Epub 2016 Nov 12 PubMed.

External Citations

  1. The Jackson Laboratory Stock# 028560
  2. The Jackson Laboratory, Stock #025636

Further Reading

No Available Further Reading