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Title: Generation of mouse models to study the role of Atg16L1 in Inflammatory Bowel Disease
Author: Arasteh, Julia Maryam
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2012
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Inflammatory Bowel Disease (IBD) refers to a group of diseases which share the common representation of chronic inflammation of the gastrointestinal tract, of which Crohn's disease and ulcerative colitis belong to. In recent years several genome wide association studies (GWA) have identified mutations in the human autophagy gene ATG16L1 (T300A) to be associated with susceptibility to Crohn's disease. This finding prompted further studies on the possible role(s) that ATG16Ll, which is one of the main components of the autophagy pathway, might have on the development of IBD. Specific mouse models were generated and in one, mice hypomorphic for Atg1611, show Paneth cell granule abnormalities and increased IL-l~ production by macrophages when infected with the Mouse Norovirus (MNV) and increased susceptibility to DSS induced colitis. ATG16Ll has also recently been shown to interact with NOD2 at the plasma membrane and this interaction is impaired in NOD2 frame shift mutations associated with Crohn's disease. Taken together these results indicate a link between Crohn's disease, autophagy, infection and innate immune function. In this Thesis the aim has been to generate three different mouse models. In one mouse model Atg1611 will be specifically knocked-out in the intestinal epithelium, the second mouse model includes the Atg1611 T300A mutation found to be associated with IBD in humans and the third mouse model lacks the WO-repeat domain of Atg1611, the function of which remains unknown. We anticipate that these mouse models will be key to understanding the role played by autophagy in inflammatory responses of the intestinal mucosa in Crohn's disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available