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.
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
- α-synuclein Inclusions
- Motor Impairment
- Mitochondrial Abnormalities
- Cognitive Dysfunction
- Neuronal Loss
- 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.
No Available Further Reading