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Genetic Diversity Between Mouse Strains Allows Identification of CC027/GeniUnc as an Orally Reactive Model of Peanut Allergy

Orgel, K;Smeekens, JM;Ye, P;Fotsch, L;Guo, R;Miller, DR;Pardo-Manuel de Villena, F;Burks, AW;Ferris, MT;Kulis, MD;

Improved animal models are needed to understand the genetic and environmental factors that contribute to food allergy. Assess food allergy phenotypes in a genetically diverse collection of mice. We selected 16 Collaborative Cross (CC) mouse strains, as well as the classic inbred C57BL/6J, C3H/HeJ, and BALB/cJ strains for screening. Female mice were sensitized to peanut intragastrically with or without Cholera toxin, then challenged with peanut by oral gavage or intraperitoneal injection, and assessed for anaphylaxis. Peanut-specific immunoglobulins, T cell cytokines, Tregs, mast cells, and basophils were quantified. Eleven of the 16 CC strains had allergic reactions to intraperitoneal peanut challenge, whereas only CC027/GeniUnc mice reproducibly experienced severe symptoms following oral food challenge (OFC). CC027/GeniUnc, C3H/HeJ, and C57BL/6J all mounted a Th2 response against peanut, leading to the production of IL-4 and IgE but only the CC027/GeniUnc mice reacted to OFC. Orally-induced anaphylaxis in CC027/GeniUnc mice was correlated with serum levels of Ara h 2 in circulation, but not with allergen-specific IgE or MMCP-1 levels, indicating systemic allergen absorption is important for anaphylaxis through the gastrointestinal tract. Furthermore, CC027/GeniUnc mice, but not C3H/HeJ or BALB/cJ, can be sensitized in the absence of Cholera toxin and react upon OFC to peanut. We have identified and characterized CC027/GeniUnc mice as a strain that is genetically susceptible to peanut allergy and prone to severe reactions following OFC. More broadly, these findings demonstrate the untapped potential of the CC population in developing novel models for allergy research. Copyright 2018. Published by Elsevier Inc.