A mouse model of walnut allergy mimics key features of the human disease

RATIONALE: Tree nut allergies are not typically outgrown and can lead to life-threatening anaphylaxis. A mouse model of walnut allergy that replicates features of the clinical condition would be a valuable tool to generate pre-clinical data for novel therapeutic approaches aimed at treating walnut and other tree nut allergies.

METHODS: A Collaborative Cross mouse strain was used to develop a mouse model of walnut allergy. Mice were sensitized to walnut once per week for four weeks by intragastric feeding of walnut extract plus cholera toxin. Mice were bled post-sensitization and allergen-specific IgE was quantified by ELISA. Finally, mice underwent oral challenges with walnut, pecan, or egg.

RESULTS: Mice sensitized to walnut produced IgE against walnut extract, the major walnut allergens Jug r 1 and Jug r 2, and pecan extract, but not to egg proteins. Walnut- and pecan-IgE were highly correlated (Spearman r=0.824, p<0.0001) as is seen in allergic patients. Oral challenges with walnut and pecan produced severe reactions with mean body temperature decreases of 5.3°C and 4.7°C, respectively, along with overt allergic symptoms including labored breathing, diarrhea, and reduced activity.

CONCLUSIONS: Walnut-sensitized mice generate IgE against the major walnut allergens, IgE cross-reacts with pecan allergens, and mice experience anaphylaxis to walnut as well as pecan, thus replicating important immunologic characteristics typical of walnut allergic patients. This model will provide a platform for developing immunotherapy for walnut and pecan allergies.