Figure 1

Sudden death in TDP-43 (A315T) mice is due to intestinal dysfunction. A: The survival of male TDP-43 (A315T) mice (median of 84 days, n = 53) differed significantly from female TDP-43 (A315T) mice (median of 126 days, n = 38) (p = 0.0004) and was for both genders very variable. B: Despite the variation in survival, the disease duration for both genders was very short: most mice died within a week after the onset of swimming gait abnormalities (median = 7 days for the males and median = 11 days for the females, n = 22 male and 15 female mice, p = 0.29). C: Comparison of intestines between NTG and TDP-43 (A315T) mice. Left: TDP-43 (A315T) mice displayed enlarged ileum (red arrowhead) and caecum (white arrow), which are easily detectable as compared to the normal-size ileum and colon from NTG mice. Right: Picture of the entire colon revealed no shortening in TDP-43 (A315T) compared to NTG mice. Note the absence of inflammatory patches or bleeding in the colon of TDP-43 (A315T) mice. D: Propulsion in colon segments from TDP-43 (A315T) and NTG mice. Recordings were made after the pellet was introduced in the colon (upper panels). Spatiotemporal map depicting the diameter of the colon segment in TDP-43 (A315T) (right) and NTG (left) mice (bar in x: 10 mm; bar in y: 100 s). E: The graphs show a significant reduction (p = 0.006) of frequency of contractions (upper graph) but not of force of muscle contraction (lower graph) between TDP-43 (A315T) (red bar) and NTG (grey bar) mice. n values indicate the number of mice from which the colon segments were analyzed.