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dc.contributor.advisorClarke, Lane L. (Lane Leroy)eng
dc.contributor.authorStrubberg, Ashlee Marioneng
dc.date.issued2016eng
dc.date.submitted2016 Summereng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis membrane conductance regulator (CFTR), a Cl- and HCO3 - channel expressed in several epithelial tissues. CF gastrointestinal (GI) disease presents several life-long complications including dybiosis, low-grade bowel inflammation and an increased risk for GI cancers. The Cftr knock-out (KO) mouse model recapitulates CF intestinal disease including hyperproliferation and the formation of intestinal polyps. Isolated intestinal epithelial cultures (enteroids) demonstrate that hyperproliferation of the Cftr KO epithelium is intrinsic to the CF epithelium as it persists in enteroid culture. Cftr KO enteroids also sustain an alkaline intracellular pH (pHi) which has been shown to stabilize the binding of the Wnt signaling mediator Disheveled (Dvl) at the plasma membrane. Cftr KO enteroids display an increase in Dvl localization and pHi at the apical membrane in crypt cells that correlates with activation of both canonical and non-canonical Wnt signaling. This study indicates a potential mechanism that increased Wnt signaling through Dvl may be a consequence of dysregulated pHi in the Cftr KO intestinal epithelium and contribute to increased proliferation and cell migration.eng
dc.identifier.urihttps://hdl.handle.net/10355/57414
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess is limited to the campuses of the University of Missouri.eng
dc.titleHyperproliferation and altered WNT signaling in the Cystic fibrosis mouse intestine.eng
dc.typeThesiseng
thesis.degree.disciplineVeterinary biomedical sciences (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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