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[Preprint]. 2023 Sep 22:2023.09.22.559064. [Version 1] doi: 10.1101/2023.09.22.559064

Figure 1. Inhibition of sortilin through AF38469 (40 nM, 400 nM, 4μM) impacts the accumulation of ASM in cell models of Batten disease.

Figure 1.

Mouse embryonic fibroblasts (MEFs) and primary cortical neurons (PNCs) were isolated from E15.5 embryos from Cln1R151X, Cln2R207X, Cln3Δex7/8, Cln6nclf, and Cln8mnd mouse lines. Cln11−/− fibroblasts were isolated from adult Cln11−/− mice. All cell lines were dosed with drug-containing media on day in vitro (DIV) 3 and DIV5 and analyzed on DIV7 using the CellInsight CX7 High-Content Screening Platform (CX7) (A) Representative ASM accumulation in Cln3Δex7/8 MEFs and PNCs. Upon treatment with AF38469 (40 nM, 400 nM, 4μM), ASM accumulation was (B-F) reduced in Cln1R151X Cln2R207X, Cln3Δex7/8, Cln6nclf, and Cln8mnd MEFs; (B-D, F) reduced in Cln1R151X Cln2R207X, Cln3Δex7/8, and Cln8mnd PNCs; and (E, G) increased in Cln6nclf PNCs and Cln11−/− MEFs. Mean ± S.E.M.. One-way ANOVA with a Šidák post-hoc test, */#p<0.05, **/##p<0.01, ***/###p<0.001, ****/####p<0.0001. Hashsigns indicate comparison to WT, asterisks indicate comparison to mutant vehicle. MEFs and PNCs n=1000-4000 and 4000-20000 cells/treatment group, respectively. Scale bar, 100 μm, Inset scale bar, 50 μm.