Figure 1. Effects of ATF4 deficiency on disease onset and life span of mutant SOD1 transgenic mice.

(A) Body weight was monitored in SOD1 transgenic mice (SOD1^G86R) on an ATF4 wild-type (ATF4^+/+) or knockout (ATF4^−/−) background. Disease onset was defined as the day when animals lost 5% of total body weight. Bottom panel: The average of disease onset with this parameter was 130 days for ATF4^+/+/SOD1^G86R (N = 15) and 183 days for ATF4^−/−/SOD1^G86R (N = 8). (B) In parallel, rotarod performance was monitored in animals presented in B. Disease onset was determined as the time when animals were not able to perform the task. With this parameter average onset was 147 days for ATF4^+/+/SOD1^G86R mice (N = 13) and 209 days for ATF4^−/−/SOD1^G86R (N = 6). Of note, two animals in each group group were excluded on this analysis because they did not learn the rotarod test. (C) Animal survival was monitored in animals described in A. Life span curves showed an average survival of 137 days for ATF4^+/+/SOD1^G86R animals (N = 15) and 155 days for ATF4^−/−/SOD1^G86R (N = 8) mice. In A-C the analysis of control ATF4^+/+ (N = 14) and ATF4^−/− (N = 4) non-transgenic (Non Tg) groups is also presented. (D) The duration of the disease was calculated by comparing the measurements of individual animals for life span and disease onset. In all graphs, mean and standard error is presented. p values were calculated with Kaplan-Meier statistics and indicated in the Figure. n.s.: non significant.