Th100 - Characterization of a Novel Casein-specific Anaphylactic Mouse Model

Eisha Ahmed – Research Institute of the McGill University Health Centre, Department of Pediatrics and Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Canada; Nicholas Vonniessen – Research Institute of the McGill University Health Centre, Department of Pediatrics and Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Canada; Casey Cohen – Research Institute of the McGill University Health Centre, Department of Pediatrics and Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Canada; Bruce Mazer – Principle investigator, Research Institute of the McGill University Health Centre, Department of Pediatrics and Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Canada

Abstract Text: Rationale: Cow’s milk allergy, caused by ingestion of proteins such as casein, is one of the leading causes of anaphylaxis in children. Mouse models that mimic anaphylaxis in humans are needed to evaluate potential new therapies for food allergy. Since severe eczema is associated with food allergy in children and may be the portal of sensitization, we established a mouse model in which the mice are transdermally sensitized.

Methods: Six- to eight-week-old male and female C57BL/6 mice (n=3-5) were exposed via gently abraded skin to dissolved casein or PBS weekly for six weeks. Two weeks after the last sensitization, all mice were challenged intragastrically with 15mg of dissolved milk powder. The challenged mice were placed in an observation chamber with live and infrared cameras to assess clinical symptoms and skin surface temperature. Following sacrifice, tissue samples including spleen, mesenteric lymph nodes, Peyer’s patches, inguinal lymph nodes, and axillary lymph nodes were assessed.

Results: Following casein sensitization, we detected casein-specific IgE in all sensitized female mice which peaked on day 28. IgE+ B cells were significantly increased in the inguinal lymph nodes of sensitized female mice compared to controls. We also observed signs of moderate anaphylactic reactions including continuous scratching and decreased reactivity in the female casein-sensitized mice.

Conclusion: These findings suggest that four weekly transdermal sensitizations were sufficient to induce systemic reactions in intragastrically challenged female C57BL/6 mice. This mouse model can serve as a preclinical model to determine the efficacy of potential treatments for food allergy.