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http://hdl.handle.net/11375/27857
Title: | Characterizing gluten immunopathology in DR3-DQ2 transgenic mice sensitized to gluten in early life |
Other Titles: | Characterizing an early life model of gluten sensitivity |
Authors: | Godbout, Julie K. |
Advisor: | Verdú, Elena F. |
Department: | Medical Sciences (Division of Physiology/Pharmacology) |
Keywords: | Celiac disease;Early life;Mouse model |
Publication Date: | 2022 |
Abstract: | The gastrointestinal tract specializes in digestion and nutrient absorption via its mucosal surface. Through this large mucosal surface, interactions between the host and its environment, including food antigens and microbes, occur. Therefore, it is imperative that the gut discriminates between innocuous food components, and potential threats such as infections. On some occasions, this fine-tuned discrimination fails, leading to chronic inflammation. Celiac disease (CeD) is an autoimmune enteropathy triggered by gluten, the name given to a family of storage proteins (prolamins) that are naturally found in wheat, barley, and rye. To develop CeD, an individual must carry the susceptibility genes, the HLA-DQ2 and/or HLA-DQ8 alleles and consume gluten. However, this is not sufficient to cause disease, indicating that environmental co-factors are at play. Individuals homozygous for the HLA-DQ2 allele are at high risk to developing CeD in infancy. Currently, there is no existing transgenic animal model that addresses early life exposure to gluten, co-factors, and their effects on CeD development. Therefore, the overall goal of my thesis is to characterize a mouse model transgenic for the HLA-DQ2 allele with exposure to gluten in early life. I first studied the physiological and immunological responses to gluten at the time of solid food introduction using DR3-DQ2 transgenic mice. I determined that after sensitization to gluten before weaning, mice developed moderate enteropathy and some developed both anti-tissue transglutaminase 2 and anti-gliadin antibodies. I then evaluated the recovery of gluten immunopathology after gluten was removed for an extended period. After 6 months on gluten-free food, enteropathy and intestinal anti-gliadin and anti-TG2 antibody levels improved. These findings show pre-weaning sensitization of DR3-DQ2 transgenic mice reproduces key features of CeD, which can be used in future studies to assess environmental triggers and mechanisms that are of importance during early life. |
URI: | http://hdl.handle.net/11375/27857 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Godbout_Julie_K_2022August_MSc.pdf | 7.28 MB | Adobe PDF | View/Open |
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