Fig. 1. Reduced mTOR signaling improves health and survival in a mouse model of Leigh syndrome.
(A) Survival of the Ndufs4−/− mice was significantly extended by rapamycin injection every other day; life span more than doubled with daily rapamycin treatment (log-rank P = 0.0002 and P < 0.0001, respectively). (B) Body weight plots of Ndufs4−/− mice. (C) Representative forelimb clasping behavior, a widely used sign of neurological degeneration. Clasping involves an inward curling of the spine and a retraction of forelimbs (shown here) or all limbs toward the midline of the body. (D and E) Clasping in vehicle-treated (D) and daily rapamycin-treated (E) Ndufs4−/− mice as a function of age. A total of 15 mice were observed for clasping daily for each treatment. Age of onset of clasping behavior is significantly delayed in rapamycin-treatedmice (**P<0.001 by log-rank test). (F) Ndufs4−/− mice show a progressive decline in rotarod performance that is rescued by rapamycin (*P < 0.05, **P < 0.005, Student’s t test; error bars are ± SEM). (See also fig. S5, which indicates replicate numbers.)