Figure 1.

(See previous page). Effects of 5-wk oral administration of cysteamine on the intestine of 2 wk-old Cftr^F508del mice. (A) Schematic representation of the effects of oral administration of cysteamine on the mortality of control (wild-type [WT] homozygotes or WT and F508del heterozygotes) and Cftr^F508del mice. (B) Cumulative survival rate in Cftr^F508del mice (n = 82) orally administered with either vehicle (n = 47) or cysteamine (n = 35) for 5 wk. Log-rank test, P = 0.0001. (C and D) Effects of cysteamine on CFTR and BECN1 protein levels in the intestine. (C) Mean changes of protein levels in 5 wild-type and 5 Cftr^F508del mice treated with either vehicle or cysteamine for 5 wk. Mean ± SD of 3 independent measurements; **P < 0.01 versus vehicle-treated Cftr^F508del mice (ANOVA). (D) Top, representative immunoblot with anti-CFTR (Abcam clone CF3) and BECN1 (Abcam clone Ab55878) in 1 mouse per treatment group. Bottom, densitometric measurement in the Cftr^F508del mouse, as percentage of vehicle-treated WT mouse normalized to TUBA levels. Mean ± SD of triplicates of independent experiments, **P < 0.01 versus vehicle-treated Cftr^F508del mice (ANOVA). (E and F) Effects of cysteamine on rectal potential difference (RPD) in response to 20 μM forskolin (Fsk) in 5 WT and 5 Cftr^F508del mice treated with vehicle or cysteamine. Measurements were conducted during continous perfusion with a Cl⁻ free solution containing 100 μM amiloride. (E) Mean changes of RPD (ΔRPD) in response to Fsk in 5 WT and 5 surviving Cftr^F508del mice. Responses in Cftr^F508del mice were significantly smaller than in wild-type mice; responses in cysteamine-treated Cftr^F508del mice were significantly higher than in vehicle-treated Cftr^F508del mice. Mean ± SD of 5 measurements in each group; ###P < 0.001 versus vehicle-treated WT mice; ° P < 0.05 versus vehicle-treated Cftr^F508del mice (ANOVA). (F) Representative response to Fsk (arrow) in one WT and one surviving Cftr^F508del mouse per treatment group.