Figure 1.
Dclk1 regulates α-Syn levels post-transcriptionally. A, Diagram of the experimental strategy. CFW WT females were bred to male WT mice. Neonatal intraventricular injections of AAVs carrying shRNA were performed on their pups, and tissue from the injected mice was collected 3 weeks following injection. The posterior cortex and associated hippocampus were dissected for Western blotting and qPCR. B, Western blot (t = 3.376, p = 0.0045) and (RNA) (t = 0.9981, p = 0.3418) for α-Syn protein (C-20) and transcript levels after Dclk1 knockdown in the mouse brain. Each data point represents individual animals. C, Tau (t = 1.457, p = 0.1713) and App (t = 0.05485, p = 0.1713) protein levels measured by Western blot after Dclk1 knockdown in the brain. Each data point represents individual animals. D, Diagram of Dclk1 transcripts and protein products expressed in the mouse brain. Numbers represent how many transcripts of each kind are expressed. The site targeted by the shRNA (exon 6 in full-length transcript, exon 2 in shortened products) is shown. E, Dclk1 protein and transcript levels in mouse brains after Dclk1 knockdown measured by Western blotting and qPCR, respectively. Protein full-length, t = 9.706, p = 0.0002; protein kinase domain, t = 4.042, p = 0.0099; RNA all, t = 7.726, p < 0.0001; RNA full-length, t = 4.798, p = 0.0001. Error bars indicate SEM. Student's t test: NS ≥ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001.