REDUCED ILEUM PERISTALTIC CONTRACTILITY IN CYSTIC FIBROSIS SWINE
Liu, Susan Lingxiu
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Cystic fibrosis (CF) is an autosomal recessive multiorgan disease caused by mutations in the gene encoding for the Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Even though CF-related lung diseases have traditionally been the main focus of both research and clinical concern, many extrapulmonary complications affect CF patient’s quality of life. With the improvements in lung health and increases in the median age of survival for CF patients, extrapulmonary complications have gained increasing attention. Abdominal complications have been reported as the most common extrapulmonary diseases in CF patients. However, the research of the underpinning causes for these clinical presentations of CF is still evolving. This study focused on testing ileum peristaltic contraction between CFTR knockout (CFTR-/- or CF) and wild-type pigs as a model using the organ bath system. We tested the contractility of the ileum ex vivo in CFTR-/- and wild-type swine immediately after birth (i.e. neonates), when the animals do not display any lung disease, and in one-week-old animals that start to develop signs of lung disease. We measured basal ileum peristalsis and the contraction induced by the agonists, acetylcholine, serotonin, and histamine. We then found that, in general, contraction in the CF ileum decreased compared to wild-type ileum right at birth and did not improve a week later. Moreover, CF pig ileum responded with a lower maximum contraction after stimulation with acetylcholine. The results support the hypothesis that the dysfunction of the CFTR channel results in reduced contraction. We hypothesize that the peristaltic contraction defect may be at the level of the intestinal smooth muscle.
DegreeMaster of Science (M.Sc.)
SupervisorIanowski , Juan
CommitteeDesai, Kaushik; Campanucci , Veronica; McKinney , Martha
Copyright DateDecember 2021