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Title: A study of tight junctions in Citrobacter rodentium infection, a mouse model of colonic inflammation
Author: Mingrino, Roberto
ISNI:       0000 0001 3410 6223
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2005
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The aim of this thesis was to study the regulation of tight junctions during inflammation of the bowel. Transmembrane proteins, Occludin, Claudin 2 and 3 and two isoforms (α⁺ and α⁻) of the peripheral membrane protein ZO-1 have been taken into consideration. In human colon a new spice variant of occluding was identified that lacks the fourth transmembrane domain. This isoforms of occluding was not detected in mouse colon. Furthermore the ratios of the transcripts of this new isoforms and the previously described alpha isoforms of ZO-1 were studied in normal and diseased human tissues. The ratio of expression of ZO-1 α⁺/α⁻ transcripts was found to be greater in surface epithelium than crypts in human and mouse colon. This may contribute to the molecular basis of permeability differences showing that the crypts are more permeable than surface epithelia as previously measured in the rat. The transmembrane protein Claudin 2 was restricted to the lower part of the crypt in the normal tissue but after two weeks C. rodentium infection, was expressed all along the crypt-villus axis. Claudin 3 was expressed all along the crypt villus axis in normal tissue and was unaffected after two weeks of infection with C. rodentium. Two homeodomain containing transcription factors Cdx1 and Cdx2, previously shown to upregulate the expression of Claudin 2 in cultured colonic epithelial cells, were studied by generating peptide-specific polyclonal antibodies. Nuclear expression of both transcription factors was reduced in C. rodentium infection suggesting that Claudin 2 expression was not increased by Cdx 1 and 2. Infection in vitro with intimin α expressing C. rodentium on T84 epithelial cells produced microcolonies and actin condensations similar to that seen in vivo.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available