Fig. 2

iTTBK1 Tg mice lose weight, exhibit motor dysfunction, and have decreased survival. a Change in weight over time of transgene induction in iTTBK1 Tg and control animals. Weight loss in iTTBK1 Tg mice began 2 weeks after removal from DOX and worsened progressively (mean ± SEM). ***p < 0.001; ****p < 0.0001. b Percent weight change from an individual animal’s initial weight while on DOX compared to their weight after 5 weeks of transgene expression. After 5 weeks after transgene induction iTTBK1 Tg animals showed marked decrease in weight. ***p < 0.001. c Latency of iTTBK1 Tg and control animals to fall from an inverted grid as a function of length of transgene expression (weeks off DOX). The iTTBK1 Tg mice showed decreasing latencies to fall over time, indicating progressive limb weakness (mean ± SEM). ****p < 0.0001. d Grip strength measurements in iTTBK1 Tg and control animals at 0, 2, 4, and 6 weeks off DOX using a dynamometer. Grip strength in iTTBK1 Tg mice declined with time after transgene induction (mean ± SEM), main effect of genotype: p = 0.069. e Increasing hind limb clasping behavior was observed in iTTBK1 Tg mice in the weeks following transgene induction (mean ± SEM). **p = 0.01, ****p < 0.0001. f iTTBK1 Tg mice have a shortened lifespan after transgene induction, with a median survival of 50 days. Control animals show no mortality during the scoring period (not plotted)