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Epithelial Ion Transport and Gastrointestinal Fluid Homeostasis

Bradford, Emily M.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1265985361

Abstract Details

2009, PhD, University of Cincinnati, Medicine : Molecular Genetics, Biochemistry, and Microbiology.
Using various knockout mouse models, the studies presented in this thesis reveal novel consequences for the loss of ion transport proteins at the cellular, organ, and systemic levels. Specifically, these studies take advantage of mice lacking NHE3, CFTR, NKCC1, NHE2, NBC4, AE2 and NBC1 to understand the functions of these proteins in vivo. In studies of CFTR-null mice, the paradigm that intestinal fluid balance is regulated predominantly by the secretory activity of CFTR is challenged, and proof-of-principle that the loss of of NHE3-mediated sodium absorption can counteract some of the effects of the loss of CFTR is established. Additionally preliminary studies in which two pharmacological inhibitors of NHE3 were tested for their ability to prevent intestinal obstructions in CFTR-null mice are described. Using NKCC1-null mice, a role for ion transport in influencing the gene expression pattern of duodenal goblet cells is proposed, and these studies show that insulin, as well as many of the pancreatic digestive enzymes, are produced by goblet cells in the mouse duodenum. Studies presented in this thesis show that Chloride Intracellular Channel 5 (CLIC5) is involved in the regulation of systemic energy metabolism and may play a minor role in gastric acid secretion in the mouse. The generation and preliminary studies of the NBC4-null mouse, for which there are currently no published phenotypes, do not show a role for NBC4 in the maintenance of basal acid-base balance and blood pressure, but do suggest an unexpected role for NBC4 in establishing heart rate. The systemic and gastrointestinal consequences of the loss of the basolateral bicarobonate transporters NBC1 and AE2 are also described.
Gary Edward Shull, PhD (Committee Chair)
Gary Dean, PhD (Committee Member)
Anil Menon, PhD (Committee Member)
Mitchell Cohen, MD (Committee Member)
Marshall Montrose, PhD (Committee Member)
259 p.
Physiological Psychology
cystic fibrosis; nhe3; fluidity; absorption; secretion; diarrhea

Recommended Citations

Citations

  • Bradford, E. M. (2009). Epithelial Ion Transport and Gastrointestinal Fluid Homeostasis [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1265985361

    APA Style (7th edition)

  • Bradford, Emily. Epithelial Ion Transport and Gastrointestinal Fluid Homeostasis. 2009. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1265985361.

    MLA Style (8th edition)

  • Bradford, Emily. "Epithelial Ion Transport and Gastrointestinal Fluid Homeostasis." Doctoral dissertation, University of Cincinnati, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1265985361

    Chicago Manual of Style (17th edition)

ucin1265985361
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© 2009, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.