{"id":{"repo_id":"missouri","oai_identifier":"oai:mospace.umsystem.edu:10355/4391"},"canonical_url":"https://search.dev.ndltd.org/etd/missouri/oai:mospace.umsystem.edu:10355/4391","repository":{"repo_id":"missouri","name":"University of Missouri","base_url":"https://mospace.umsystem.edu/oai/request"},"display":{"title":"The cystic fibrosis transmembrane conductance regulator and acid-base transporters of the murine duodenum","abstract":"The alkaline mucus barrier of the duodenum plays an important role in protecting the epithelium from acidic chyme entering from the stomach. Active HCO₃⁻ secretion involves the apical membrane activities of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel, the protein that is defective in cystic fibrosis (CF), and Cl⁻/HCO₃⁻ exchangers. Under basal conditions, studies of CF patients and mouse models indicate that HCO₃⁻ secretion by anion exchange predominates. In addition, basal HCO₃⁻ secretion is reduced in the CF duodenum, but the specific pathophysiology for this deficiency has yet to be elucidated. Our studies reveal that Cl⁻ channel activity by CFTR facilitates apical membrane Cl⁻in/HCO₃⁻out exchange by providing a Cl⁻ 'leak' and is responsible for the reduced rate of Cl⁻/HCO₃⁻ exchange in the murine CF intestine. Using mice with gene-targeted deletions of the apical membrane Cl⁻/HCO₃⁻ exchangers PAT-1, DRA, and AE4, PAT-1 was found to be the major Cl⁻/HCO₃⁻ exchanger of the upper villus of the duodenum. Interestingly, these studies also revealed a novel role for PAT-1 as a base-importer (i.e., Cl⁻out/HCO₃⁻in) whereby it interacts with carbonic anhydrase II (CAII), the most widely expressed isozyme of the small intestine, during H⁺/peptide transport to minimize intracellular acidification and sustain nutrient absorption.","abstract_html":"The alkaline mucus barrier of the duodenum plays an important role in protecting the epithelium from acidic chyme entering from the stomach. Active HCO₃⁻ secretion involves the apical membrane activities of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel, the protein that is defective in cystic fibrosis (CF), and Cl⁻/HCO₃⁻ exchangers. Under basal conditions, studies of CF patients and mouse models indicate that HCO₃⁻ secretion by anion exchange predominates. In addition, basal HCO₃⁻ secretion is reduced in the CF duodenum, but the specific pathophysiology for this deficiency has yet to be elucidated. Our studies reveal that Cl⁻ channel activity by CFTR facilitates apical membrane Cl⁻in/HCO₃⁻out exchange by providing a Cl⁻ 'leak' and is responsible for the reduced rate of Cl⁻/HCO₃⁻ exchange in the murine CF intestine. Using mice with gene-targeted deletions of the apical membrane Cl⁻/HCO₃⁻ exchangers PAT-1, DRA, and AE4, PAT-1 was found to be the major Cl⁻/HCO₃⁻ exchanger of the upper villus of the duodenum. Interestingly, these studies also revealed a novel role for PAT-1 as a base-importer (i.e., Cl⁻out/HCO₃⁻in) whereby it interacts with carbonic anhydrase II (CAII), the most widely expressed isozyme of the small intestine, during H⁺/peptide transport to minimize intracellular acidification and sustain nutrient absorption.","abstract_has_math":false,"creators":["Simpson, Janet Elizabeth, 1976-"],"institution":"University of Missouri--Columbia","degree_name":"Ph. D.","degree_level":"Doctoral","degree_discipline":"Veterinary biomedical sciences (MU)","degree_department":null,"school":null,"contributors":[],"advisors":["Clarke, Lane L. (Lane Leroy)"],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006","date_published":"2006","updated_at":"2026-07-24T03:07:57Z","subjects":[],"languages":["eng","English"],"rights":["OpenAccess."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.32469/10355/4391"],"render_values":[{"text":"https://doi.org/10.32469/10355/4391","href":"https://doi.org/10.32469/10355/4391","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10355/4391","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Clarke, Lane L. (Lane Leroy)"]},{"key":"dc:creator","label":"Author","values":["Simpson, Janet Elizabeth, 1976-"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2010-01-12T17:06:19Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2010-01-12T17:06:19Z"]},{"key":"dc:date.issued","label":"Date","values":["2006"]},{"key":"dc:publisher","label":"Institution","values":["University of Missouri--Columbia"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Veterinary biomedical sciences (MU)"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph. D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Missouri--Columbia"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["OpenAccess."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.32469/10355/4391"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10355/4391"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.","Vita.","\"August 2006\"","Includes bibliographical references.","Thesis (Ph. D.) University of Missouri-Columbia 2006.","Dissertations, Academic -- University of Missouri--Columbia -- Veterinary biomedical sciences."]},{"key":"dc:description.abstract","label":"Abstract","values":["The alkaline mucus barrier of the duodenum plays an important role in protecting the epithelium from acidic chyme entering from the stomach. Active HCO₃⁻ secretion involves the apical membrane activities of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel, the protein that is defective in cystic fibrosis (CF), and Cl⁻/HCO₃⁻ exchangers. Under basal conditions, studies of CF patients and mouse models indicate that HCO₃⁻ secretion by anion exchange predominates. In addition, basal HCO₃⁻ secretion is reduced in the CF duodenum, but the specific pathophysiology for this deficiency has yet to be elucidated. Our studies reveal that Cl⁻ channel activity by CFTR facilitates apical membrane Cl⁻in/HCO₃⁻out exchange by providing a Cl⁻ 'leak' and is responsible for the reduced rate of Cl⁻/HCO₃⁻ exchange in the murine CF intestine. Using mice with gene-targeted deletions of the apical membrane Cl⁻/HCO₃⁻ exchangers PAT-1, DRA, and AE4, PAT-1 was found to be the major Cl⁻/HCO₃⁻ exchanger of the upper villus of the duodenum. Interestingly, these studies also revealed a novel role for PAT-1 as a base-importer (i.e., Cl⁻out/HCO₃⁻in) whereby it interacts with carbonic anhydrase II (CAII), the most widely expressed isozyme of the small intestine, during H⁺/peptide transport to minimize intracellular acidification and sustain nutrient absorption."]},{"key":"dc:title","label":"Title","values":["The cystic fibrosis transmembrane conductance regulator and acid-base transporters of the murine duodenum"]}]}],"canonical_facts":{"dc:contributor.advisor":["Clarke, Lane L. (Lane Leroy)"],"dc:creator":["Simpson, Janet Elizabeth, 1976-"],"dc:date.accessioned":["2010-01-12T17:06:19Z"],"dc:date.available":["2010-01-12T17:06:19Z"],"dc:date.issued":["2006"],"dc:description":["The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.","Vita.","\"August 2006\"","Includes bibliographical references.","Thesis (Ph. D.) University of Missouri-Columbia 2006.","Dissertations, Academic -- University of Missouri--Columbia -- Veterinary biomedical sciences."],"dc:description.abstract":["The alkaline mucus barrier of the duodenum plays an important role in protecting the epithelium from acidic chyme entering from the stomach. Active HCO₃⁻ secretion involves the apical membrane activities of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel, the protein that is defective in cystic fibrosis (CF), and Cl⁻/HCO₃⁻ exchangers. Under basal conditions, studies of CF patients and mouse models indicate that HCO₃⁻ secretion by anion exchange predominates. In addition, basal HCO₃⁻ secretion is reduced in the CF duodenum, but the specific pathophysiology for this deficiency has yet to be elucidated. Our studies reveal that Cl⁻ channel activity by CFTR facilitates apical membrane Cl⁻in/HCO₃⁻out exchange by providing a Cl⁻ 'leak' and is responsible for the reduced rate of Cl⁻/HCO₃⁻ exchange in the murine CF intestine. Using mice with gene-targeted deletions of the apical membrane Cl⁻/HCO₃⁻ exchangers PAT-1, DRA, and AE4, PAT-1 was found to be the major Cl⁻/HCO₃⁻ exchanger of the upper villus of the duodenum. Interestingly, these studies also revealed a novel role for PAT-1 as a base-importer (i.e., Cl⁻out/HCO₃⁻in) whereby it interacts with carbonic anhydrase II (CAII), the most widely expressed isozyme of the small intestine, during H⁺/peptide transport to minimize intracellular acidification and sustain nutrient absorption."],"dc:identifier.doi":["https://doi.org/10.32469/10355/4391"],"dc:identifier.uri":["https://hdl.handle.net/10355/4391"],"dc:language":["English"],"dc:language.iso":["eng"],"dc:publisher":["University of Missouri--Columbia"],"dc:rights":["OpenAccess."],"dc:title":["The cystic fibrosis transmembrane conductance regulator and acid-base transporters of the murine duodenum"],"dc:type":["Thesis"],"thesis:degree_discipline":["Veterinary biomedical sciences (MU)"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["University of Missouri--Columbia"]},"updated_at":"2026-07-24T03:07:57Z"}