Figure 4.

Motor domain remains unaltered after 2 weeks of suppression of hTDP-43-WT transgene. (A–D) Open-field task; locomotor and exploratory behaviors were preserved in suppressed hTDP-43-WT mice. (A) Occupancy plot. Representative heat maps for time spent by subject mice during the entire session are shown. The heat map was constructed based on body position. (B) Total distance traveled. (C) Total distance traveled in time segments of 5 min. (D) Relative center distance. No significant differences were found between controls and bigenic animals in locomotion or exploration. (E) Motor coordination and balance were not affected after suppression of hTDP-43-WT expression. Accelerated rotarod performance (4–40 rpm/5 min): four trials per test were performed during the test day with a 2-min interval between trials. Latency to fall off the apparatus was recorded. (F–G) No signs of spasticity or motor strength deficits are detected in suppressed hTDP-43-WT mice. (F) The absence of clasping phenotype in both 0.5 month and 1 month (sup) mice. Percentage of animals positive for abnormal clasping and number of animals positive/total tested are shown. (G) Hanging wire grip test. Grip strength was assessed using a standard wire cage turned upside down. The latency to fall off the wire lid was quantified; a 60-s cutoff time was used. No significant differences were found between control and bigenic animals [p > 0.05 Student’s t test in (B,D), Mann-Whitney U test in (G), repeated-measures ANOVA in (C,E), Fisher’s exact test in (F)]. n = 12, 15 for control and bigenic 0.5 month mice, respectively; n = 12, 14 for control and bigenic 1 month (sup) mice, respectively. Data represent mean ± SEM.