Fig. 8

Co-expression of TDP-43^WT and TDP-43^Q331K in mice results in an increase in cytoplasmic and insoluble TDP-43. a Western blotting of nuclear and cytosolic fractions from brains demonstrated an increase in cytosolic and nuclear TDP-43 levels in young transgenic animals compared to their non-transgenic littermates. GAPDH was used as the marker for the cytosolic fraction, and Lamin B1 for the nuclear fraction. b Quantification of cytosolic TDP-43 levels (using the bands indicated in the red boxes), showing an expression and mutation dependent increase in TDP-43 levels in all transgenic animals (** p < 0.001 vs. NTg; †p < 0.05; ††p < 0.001 vs. TDP-43^WT, #p < 0.05 vs. TDP-43^Q331K). c Quantification of nuclear TDP-43 levels (using the bands indicated in the red boxes), showing a similar increase in TDP-43 in all transgenic animals, regardless of mutation status (* p < 0.05 vs. NTg). d Western blotting of detergent fractionation of brain demonstrated an increase in soluble and insoluble TDP-43 in all transgenic animals. This increase was more pronounced in TDP-43^WTxQ331K and TDP-43^Q331K animals. e Quantification of detergent soluble and insoluble TDP-43 levels, showing a significant increase in TDP-43 in all fractions in TDP-43^WTxQ331K animals compared to NTg littermates, and in the insoluble urea fraction, compared to all other animals. Insoluble TDP-43 was also significantly increased in the urea fraction of TDP-43^Q331K single transgenic animals, as was soluble TDP-43 detected in the high salt fraction. (* p < 0.05; ** p < 0.001 vs. non-transgenic animals; †p < 0.05; †p < 0.001 vs. TDP-43^WT animals; #p < 0.05 vs. TDP-43^Q331K animals)