A hallmark of cystic fibrosis, a disease caused by mutations in the CTFR gene, is the accumulation of abnormally thick and sticky mucus in the lung, intestine, and various other organs. Although the accumulation of this mucus is thought likely to play a central role in the development of disease, how mutations in the CTFR gene lead to mucus accumulation have not been determined.
However, Paul Quinton and colleagues, at the University of California at San Diego, La Jolla, have now provided insight into this issue by studying mouse small intestine segments ex vivo, according to a paper to be published in the August 24 issue of the Journal of Clinical Investigation. In an accompanying commentary, Robert DeLisle, at the University of Kansas School of Medicine, Kansas City, highlights the importance of the study and the potential new take on how mutations in the CTFR gene lead to mucus accumulation and disease.
One of the functions of the CTFR protein generated by the nonmutated CTFR gene is to transport bicarbonate (HCO3–) out of cells. In their study, Quinton and colleagues developed a new ex vivo system for monitoring mucus release from the mouse small intestine to investigate whether defects in this function of CFTR might affect mucus secretion. Although basal rates of mucus release were similar in the presence or absence of bicarbonate, mucus release stimulated by natural chemicals such as serotonin was markedly decreased in the absence of bicarbonate. Interestingly, in a mouse model of cystic fibrosis, mucus release stimulated by natural chemicals was minimal in the presence or absence of bicarbonate. The authors therefore suggest that normal mucus release requires concurrent bicarbonate secretion and that the abnormally thick and sticky mucus that characterizes cystic fibrosis might be caused by defective bicarbonate secretion.
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