Development of MAPT S305 mutation models exhibiting elevated 4R tau expression, resulting in altered neuronal and astrocytic function [Targeted MAPT ISO-seq]

We have developed a panel of isogenic iPSC lines carrying MAPT splice-site mutations S305S, S305I or S305N, derived from four different donors. All three mutations significantly increased the proportion of 4R tau expression in iPSC-neurons and astrocytes, with up to 80% 4R transcripts in S305N neurons from as early as 4 weeks of differentiation. Overall design: iPSCs were differentiated into neurons (4, 6 and 8 weeks of differentiation) and astrocytes, and submitted for targeted MAPT ISO-seq