Current murine models of peanut allergy react on intraperitoneal challenge but fail to react on oral challenge, making them less physiologically relevant. However, a recently identified inbred mouse strain from the Collaborative Cross (CC) experiences a severe, systemic reaction on oral challenge. Differences between common lab strains and CC mice were characterized to determine which feature makes CC mice reactive.
C3H/HeJ, C57BL/6J, and CC females were sensitized intragastrically at 4-6 weeks of age with peanut extract and cholera toxin for 4 weeks and then challenged intragastrically with peanut extract. Mice were bled one week post-sensitization and 60 minutes after challenge. Serology and Ara h 2 (Ah2) absorption were compared between strains.
Within 15 minutes of challenge a significant decrease in body temperature was observed in CC mice, (n=12; mean: -2.8°C; range: 0.7-5.3°C) with no change in C3H/HeJ or C57BL/6J. Peanut-specific IgE (PNsIgE) and PNsIgG1 were significantly higher in CC mice compared to C3H/HeJ (p<0.05) but no different from C57BL/6J. PNsIgE did not correlate with reaction severity in CC mice. The major peanut component, Ah2 was detectable in the serum of CC and C57BL/6J, but not C3H/HeJ mice after challenge. However, serum quantities of Ah2 were significantly greater in CC mice compared to C57BL/6J (p<0.05), and serum Ah2 levels correlated with reaction severity (r2=0.5217, p=0.0011) in CC mice.
CC mice are an improved animal model of peanut allergy. Ah2 absorption into the circulation is correlated with systemic reactions in mice, and could be an important factor in humans experiencing severe reactions.