2008 Progress Report: Improved Animal Model for Assessment of Allergenic Potential of Foods Through Selective Deletion of T Cells and Global Gene Expression AnalysisEPA Grant Number: R833134
Title: Improved Animal Model for Assessment of Allergenic Potential of Foods Through Selective Deletion of T Cells and Global Gene Expression Analysis
Investigators: HogenEsch, Harm , Muir, William
Institution: Purdue University
EPA Project Officer: McOliver, Cynthia
Project Period: November 1, 2006 through October 31, 2009 (Extended to November 30, 2010)
Project Period Covered by this Report: August 1, 2008 through March 1,2009
Project Amount: $398,497
RFA: Biotechnology: Potential Allergenicity of Genetically Engineered Foods (2006) RFA Text | Recipients Lists
Research Category: Food Allergy , Health
The overall objective of the study is to develop a new animal model to test for allergenic potential of foods that requires a short duration of testing, has increased sensitivity and discriminatory power over existing models, and is relatively easy to use.
The specific objectives of this proposal are to:
(1) determine if mice that lack a subpopulation of T lymphocytes known as TCRγδ+ T cells, are more sensitive to food allergens than mice with an intact TCRγδ+ T cell population. Previous studies indicate that TCRγδ+ T cells are important for the maintenance of oral tolerance suggesting that their absence will make the mice more sensitive to food allergens;
(2) determine if oral administration of food proteins to TCRγδ-deficient mice can discriminate between allergenic and non-allergenic proteins; and
(3) identify early biomarkers of food allergenicity in mice that shorten the exposure protocol and increase the sensitivity of the mouse model.
Previous year studies had identified the A/J mice as a strain that selectively produces high levels of IgE in response to feeding known allergens (peanut protein extract and ovalbumin) and not in response against non-allergenic proteins such as potato protein and spinach protein extract. Additional studies indicate that the A/J mice are responsive to doses as low as 0.1 mg, at least 10 times lower than the usual dose used in food allergy studies.
RNA has been isolated from the spleen, duodenum, and mesenteric lymph node of A/J mice fed with peanut protein extract and cholera toxin. The expression of > 20,000 genes is being analyzed by hybridization with Affymetrix microarrays.
The A/J model will be used to identify novel biomarkers for early detection of food allergy. For this purpose, mice will be fed allergenic and non-allergenic proteins, and RNA will be extracted from tissues and compared for gene expression using DNA microarrays.