Figure 6.
Effect of 9 on the pre-mRNA splicing outcome of tau exon 10 in primary neurons harvested from human tau transgenic mice (htau mice). (Top) Primary neurons were extracted and cultured from htau mice brains as described in Experimental Section. Total RNA was extracted after 48 h with treatment of DMSO (vehicle), 4R- to-3R ASO, or a Scrambled ASO control (“Scrambled”). The 4R/3R ratio, which was calculated as 4R tau mRNA expression divided by 3R tau mRNA expression, was measured by RT-qPCR. (Bottom) Compound 9 downregulated 4R/3R ratio dose-dependently, up to 50%. The 4R-to-3R ASO decreased 4R/3R ratio by 80%, whereas the scrambled ASO had no effect. Error bars indicate SD.