Project Leader: Daniel Vargas

In a collaborative study with Dr. Tim Moran that we conducted to identify new mouse models of allergic asthma, we found that mice from one particular Collaborative Cross strain, CC011, exhibited truly extreme responses to house dust mite allergen, with very high numbers of eosinophils in the airspaces, elevated lung resistance, and extensive airway wall remodeling. Additionally, treatment with steroids did not ameliorate airway inflammation. As such, we propose that this is a new model of severe asthma. Which genes in the CC011 genome confer susceptibility to developing this phenotype? How do those genes affect the development of allergic inflammation and resistance to steroids? These are the questions we aim to answer.

CC011 mice chronically exposed to HDM exhibit histological features of severe asthma. (A) Representative cross-sections of large airway from CC011 control mice exposed to PBS (top row) or HDM (bottom row) for 5 weeks. Large airway stained with (from left to right) with H&E, Alcian Blue-Periodic Acid-Schiff (AB-PAS), Mason’s Trichrome (MT), and α-smooth muscle actin (SMA) by immunohistochemistry. Scale bars = 50uM. (B-D) Additional abnormalities in HDM treated mouse shown in A with H&E staining. (B) H&E of whole lung cross-section. Scale bar = 500uM. (C) Higher magnification image of airway with arrowheads pointing to extracellular crystals. Scale bars = 50uM. (D) Higher magnification image with arrowheads indicating submucosal mast cells. Scale bar = 10uM.