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.
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.
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.
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.
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Dopamine Deficiency
- Non-Motor Impairment
- α-synuclein Inclusions
- Motor Impairment
- Mitochondrial Abnormalities
- Neuronal Loss
Last Updated: 07 Feb 2019
- Ninkina N, Connor-Robson N, Ustyugov AA, Tarasova TV, Shelkovnikova TA, Buchman VL. 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.
- Roman AY, Limorenko G, Ustyugov AA, Tarasova TV, Lysikova EA, Buchman VL, Ninkina N. 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.
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