<p><b>A.</b> Representative Isc tracing of ileum from homozygous mutant F508del mice in the Ussing-chamber before (t = 0 h) and after treatment with the proteasome inhibitor ALLN (t = 6 h). Residual forskolin and genistein mediated chloride secretion at the start of the experiment (t = 0 h) was observed in all experiments. The dotted line indicates the average short circuit current level following forskolin/genistein addition for WT ileum (N = 24). ALLN treatment resulted in complete correction of CFTR activity compared to wild type. <b>B.</b> Ileal mucosa from F508del/F508del mutant mice was mounted in Ussing- chamber holders and incubated under carbogen gassing in William's E medium for 4 h at 37°C in the presence of vehicle (DMSO, 0.1%), MG-132 (10 µM), epoxomicin (1 µM ), PS341 (30 nM) or ALNN (20 µM). Subsequently the Isc response to forskolin <i>plus</i> genistein was measured in Ussing chambers. <b>C.</b> At the end of each measurement the viability of each sample was tested by addition of 10 mM glucose to the mucosal bath. The average glucose response after treatment with the various proteasome inhibitors is not significantly different from the vehicle control. All experiments were performed with N = 4 mice, two samples per mouse. Averages plus or minus SD are shown, statistical analysis was by one way ANOVA with Tukey post hoc test for multiple averages, *: indicates significantly different P<0.05 from vehicle).</p
