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. Author manuscript; available in PMC: 2022 Oct 1.
Published in final edited form as: Mol Psychiatry. 2022 Feb 23;27(4):1970–1989. doi: 10.1038/s41380-022-01454-5

Figure 3. Normalization of copy number of APP or DYRK1A, but not RCAN1 and SYNJ1, rescues elevated phosphorylated tau levels in T21 neurons.

Figure 3.

IPSC lines targeted at each of the candidate HSA21 loci were differentiated to neuronal fate in parallel to T21 iPSCs and analyzed at d21. Control T21 iNs in these comparisons had been exposed to the same CRISPR targeting pipeline as the targeted lines, but mutations at the targeted locus were not introduced. Three differentiation rounds were performed with three wells analyzed per genotype per differentiation. For each, media were collected for Aβ quantification via ELISA and cells lysed for WB at d21. Shown is a representative WB and quantifications of data collected for targeting at each locus: APP (a,b), DYRK1A (c,d), RCAN1 (e,f), and SYNJ1 (g,h). “Total tau” quantification is determined using the K9JA antibody. One-way ANOVA with Dunnett’s multiple comparison’s test, *p<0.05; **p<0.01; ***p<0.005; ****p<0.001.