Fig. 5.

Rescue of ΔF508-CFTR in intestinal organoids from ΔF508/ΔF508 mice. A–D, Rescue of ΔF508-CFTR with SU5402 analyzed in intestinal organoids from ΔF508/ΔF508 mice by organoids swelling: A and B, Intestinal organoids derived from crypts isolated from the terminal ileum of ΔF508 mice (and WT littermate controls) were treated (at 37 °C) with 5 μm forskolin for 50 min to activate CFTR, leading to swelling via chloride efflux and lumenal fluid accumulation by WT-CFTR but not ΔF508-CFTR. Scale bars = 50 μm. C, ΔF508 organoids do not exhibit increased surface area following forskolin treatment, but swelling can be rescued at low temp: As in B, except one batch of ΔF508 organoids were preincubated at 27 °C for 24 h prior to assay, revealing temp. rescue. D, Treatment with SU5402 or VX-809 partially rescued swelling in ΔF508-CFTR organoids. ΔF508 organoids were pretreated with VX-809 (3 μm; green) or SU-5402 (10 μm; red), administered to the organoid culture media. Treatment with either compound (at 37 °C) partially rescued CFTR-mediated swelling in the ΔF508 organoids, a rescue augmented by combining both SU5402 and VX-809. Error bars for panels B–D represent mean ± S.D. n = 20–30 organoids per treatment. Forsk: Forskolin.