TY - JOUR T1 - LSC 2013 abstract - Characterization of Tbx21-deficient mice as a model for transgenerational asthma risk propagation JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - PP137 AU - Stefan Dehmel AU - Petra Nathan AU - Katrin Milger AU - Rabea Imker AU - Oliver Eickelberg AU - Susanne Krauss-Etschmann Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/PP137.abstract N2 - Background: Maternal asthma is a known risk factor for developing asthma later in life, but the underlying molecular mechanisms are not well understood. Thus, we characterized a model for in utero exposure to maternal genetic asthma predisposition, mimicking the human situation more closely than standard allergen exposure models. Asthma patients show a distinct decrease of pulmonary T cells expressing the Th1-specific transcription factor TBX21 (T-BET). In addition, Tbx21-deficient mice spontaneously develop airway changes reminiscent of human asthma.Aim: To study the potential of Tbx21-deficient mice as a transgenerational model for asthma risk propagation.Methods: Wild type (WT), Tbx21+/- (HZ) and Tbx21-/- (KO) C57BL/6J mice were analyzed for asthma-related parameters at different ages (MWU test: *: p<0.05, **: p<0.01, ***: p<0.001).Results: No differences were observed in mice at 10w of age. PAS staining of lung sections revealed an increased amount of mucus-producing goblet cells in 20w old KO** and 30w old HZ** and KO*** mice compared to WT mice. At 30w, BALF macrophages were decreased in HZ* and KO**, while BALF eosinophils were increased in KO** mice compared to WT mice. Lung inflammatory infiltrates were increased in 30w old HZ and KO mice compared to WT mice. Prominent vascular remodeling with increased alpha-SMA deposition was observed in 30w old HZ and KO mice. Further characterization of age-dependent disease progression including lung function and analysis of pulmonary cytokine levels is ongoing.Conclusion: These first results indicate the applicability of Tbx21-deficient mice to study the molecular mechanisms underlying transgenerational asthma risk propagation. ER -