Figure 3.

Improvement of life span, body weight loss, and rotarod performance in AAV-Npc1^−/− mice. (A) Kaplan–Meier survival curve. The average life span of untreated-Npc1^−/− without gel feeding was 75 days (63–86 days), but both untreated and saline-treated Npc1^−/− with gel feeding survived for an average of 100 days (88–111 days) and 98 days (82–116 days), respectively. The average life span was prolonged by ∼25 days simply by gel feeding. AAV-treated Npc1^−/− mice lived for 205 days (100–310 days) on average, which was 105 days longer than untreated and saline-treated Npc1^−/− mice with gel feeding. The maximum life span of AAV-treated Npc1^−/− reached 310 days. (B) Body weight changes. We assessed the body weight of every mouse weekly and plotted the average of each group from weeks 5 to 25. However, there were marked differences between the groups at the starting point. All three untreated Npc1^−/− mice groups lost body weight rapidly from weeks 5 to 7 until they died, whereas the AAV-treated Npc1^−/− mice showed a body weight gain until week 15 and thereafter showed a slight body weight loss. (C–E) The rotarod performance. We compared the motor function between AAV- and saline-treated mice using the rotarod test. (C) The average time of each group spent on the rotarod is indicated on the graph. The time from the starting point at week 5 in the saline-treated Npc1^−/− mice rapidly deteriorated, reaching 0 s at week 11. AAV-treated Npc1^−/− mice maintained their performance for much longer, and no mice showed a time of 0 s at week 11. However, their times gradually declined over the course. D and E show the results of statistical analyses at weeks 8 and 9, respectively. (D), (E) The time spent on the rod was not significantly different between the AAV-treated Npc1^+/+ versus Npc1^−/−, but it was significant different between the AAV-treated Npc1^−/− versus Npc1^−/− mice. ns, not significant; ***p < 0.001; **p < 0.01.