Fig. 1.
Age-dependent ALS-like phenotypes of Heterozygous male N390D/+mice. a Schematic diagram of targeted knock-in (KIN) of ALS-associated mutant TDP-43, A315T (green star) and N390D (red star), in mouse Tardbp gene. Both sides of the NEO cassette in the targeted allele (TardbpNEO) was flanked by lox P sequence (arrowhead). The genotypes of mice carrying the different knock-in allele (TardbpKIN) were validated by PCR, as exemplified for two heterozygous lines each for N390D and A315T. #125 plus #180 and #108 plus #361 are the name of mouse lines of A315T and N390D, respectively. For more details, see Methods. b The survival rates of two lines each of A315T/+ (right panel) and N390D/+ male mice (left panel) are compared to their +/+ littermates. Note the significantly shorter life span of N390D/+ male mice, but not A315T/+ male mice, than the +/+ male mice. *p < 0.05. c Comparison analysis of the average body weight of the remains of N390D/+ male mice to that of the living mice weighed before they died. The left panel shows the comparison of the weight of remains between +/+ and N390D/+ male mice in a manner consistent with the survival curve. The right panel shows the comparison of the body weight of the remains of N390D/+ male mice to the body weight recorded when they are still alive. * p < 0.05. The numbers (N) of mice analyzed per group are listed in the figure