JCI - Differential roles of NHERF1, NHERF2, and PDZK1 in regulating CFTR-mediated intestinal anion secretion in mice

Differential roles of NHERF1, NHERF2, and PDZK1 in regulating CFTR-mediated intestinal anion secretion in mice

Anurag Kumar Singh, Brigitte Riederer, Anja Krabbenhöft, Brigitte Rausch, Janina Bonhagen, Ulrich Lehmann, Hugo R. de Jonge, Mark Donowitz, Chris Yun, Edward J. Weinman, Olivier Kocher, Boris M. Hogema, Ursula Seidler

Published in Volume 119, Issue 3

J Clin Invest. 2009; 119(3):540–550 doi:10.1172/JCI35541

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Figure 8

Basal bicarbonate secretion and FSK-stimulated peak secretory response in Pdzk1^–/–, Pdzk1^–/–Cftr^–/–, Nherf1^–/–Pdzk1^–/–, and Nherf1^–/–Nherf2^–/–Pdzk1^–/– duodenum.

(A and B) Basal duodenal HCO₃^– secretion was significantly reduced in Pdzk1^–/– mice compared with WT littermates (n = 7). In A, the 20-min application time is denoted by shading. *P < 0.01, **P < 0.001 versus WT; ^#P < 0.01, ^##P < 0.001, ^###P < 0.001 versus basal value; ^†P < 0.01, ^††P < 0.001 versus Pdzk1^–/–. (B) The response to FSK was not altered in Pdzk1^–/– mice, but was virtually abolished in Pdzk1^–/–Cftr^–/– mice. (C) The additional deletion of Nherf2 resulted in a higher basal HCO₃^– secretory rate than in Nherf1^–/– and Nherf1^–/–Pdzk1^–/– mice, congruent with the results in Nherf2^–/– and Nherf1^–/–Nherf2^–/– mice. (D) The defect in FSK stimulation resulting from absence of Nherf1 was the dominant disturbance in the Nherf1^–/–Pdzk1^–/– and Nherf1^–/–Nherf2^–/–Pdzk1^–/– mice. (B–D) *P < 0.05; ***P < 0.001.