Additional Disruption of the ClC-2 Cl- Channel Does Not Exacerbate the Cystic Fibrosis Phenotype of Cystic Fibrosis Transmembrane Conductance Regulator Mouse Models

Basolateral localization of native ClC-2 chloride channels in absorptive intestinal epithelial cells and basolateral sorting encoded by a CBS-2 domain di-leucine motif

“…ClC-2 could provide the basolateral Cl -conductance in electroneutral salt and water absorption (Catalán et al, 2002;Lipecka et al, 2002;Catalán et al, 2004). Such a function would explain the results in double CFTR/ClC-2 knockout mice, which appear to survive better than CFTR-deficient mice (Zdebik et al, 2004).…”

“…ClC-2 knockout mouse models present blindness and male infertility and, it has been argued, transepithelial transport defects could be responsible for these alterations (Bösl et al, 2001;Nehrke et al, 2002). Dual ClC-2 and CFTR knockout mice do not exhibit a worsening of the CF phenotype, suggesting indirectly that ClC-2 does not contribute to secretion and might, therefore, not be located apically (Zdebik et al, 2004).…”

Chloride channel diseases resulting from impaired transepithelial transport or vesicular function

“…It is not significantly expressed in deeper sites of crypts, where CFTR is expressed (10). These findings, and in particular the CFTR/ClC-2 double-KO mice (24), should put an end to speculations that ClC-2 activation may ameliorate the cystic fibrosis phenotype.…”

Erratum

“…Lubiprostone received approval from the United States Food and Drug Administration in 2006 under the trade name AMITIZA ® for the long-term treatment of chronic idiopathic constipation in adults (5). The approved labeling specifically includes a contraindication to lubiprostone's use in severe diarrhea.…”