title: Loss of Slc26a9 anion transporter alters intestinal electrolyte and HCO3(-) transport and reduces survival in CFTR-deficient mice.
abstract: Slc26a9 is an anion transporter that is strongly expressed in the stomach and lung. Slc26a9 variants were recently found associated with a higher incidence of meconium ileus in cystic fibrosis (CF) infants, raising the question whether Slc26a9 is expressed in the intestine and what its functional role is. Slc26a9 messenger RNA (mRNA) was found highly expressed in the mucosae of the murine and human upper gastrointestinal tract, with an abrupt decrease in expression levels beyond the duodenum. Absence of SLC26a9 expression strongly increased the intestinally related mortality in cystic fibrosis transmembrane conductance regulator (CFTR)-deficient mice. Proximal duodenal JHCO3(-) and fluid secretion were reduced in the absence of Slc26a9 expression. In the proximal duodenum of young Slc26a9 KO mice, the glands and villi/crypts were elongated and proliferation was enhanced. This difference was lost with ageing, as were the alterations in fluid movement, whereas the reduction in JHCO3(-) remained. Laser dissection followed by qPCR suggested Slc26a9 expression to be crypt-predominant in the duodenum. In summary, deletion of Slc26a9 caused bicarbonate secretory and fluid absorptive changes in the proximal duodenal mucosa and increased the postweaning death rates in CFTR-deficient mice. Functional alterations in the duodenum were most prominent at young ages. We assume that the association of meconium ileus and Slc26a9 variants may be related to maldigestion and impaired downstream signaling caused by loss of upper GI tract digestive functions, aggravating the situation of lack of secretion and sticky mucus at the site of obstruction in CF intestine.
authors: Department of Gastroenterology, Hannover Medical School, Hannover, Germany.
authors: Xuemei
authors: X
authors: Liu
authors: Taolang
authors: T
authors: Li
authors: Brigitte
authors: B
authors: Riederer
authors: Henrike
authors: H
authors: Lenzen
authors: Lisa
authors: L
authors: Ludolph
authors: Sunil
authors: S
authors: Yeruva
authors: Biguang
authors: B
authors: Tuo
authors: Manoocher
authors: M
authors: Soleimani
authors: Ursula
authors: U
authors: Seidler
mesh_terms: D000818:Animals; D017920:Antiporters / Q000235:genetics* / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism*; D049109:Cell Proliferation; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004386:Duodenum / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D017136:Ion Transport; D051379:Mice; D008810:Mice, Inbred C57BL; D000076988:Sulfate Transporters
chemical_list: D017920:Antiporters; D001639:Bicarbonates; C533708:Slc26a9 protein, mouse; D000076988:Sulfate Transporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator