Phenotypes for Stat3 Tg(SFTPC-rtTA)5Jaw Tg(tetO-cre)1Jaw MGI:4888972 MGI Mouse

mortality/aging ( J:87622 )

N	• under normoxic conditions, mice treated with doxycycline from E0 to P25 exhibit no differences in survival at E18.5 or after birth relative to control littermates

abnormal cytokine level ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display increased IL-1beta, IL-6, and MIP-2 levels in lung tissue relative to control littermates

increased susceptibility to hyperoxia-induced injury ( J:87622 )

• when doxycycline is administered from E0 to P25, adult mice are more susceptible to hyperoxia-induced (95% O2 for 65 hrs) lung injury than oxygen-exposed control littermates, displaying an earlier onset of respiratory symptoms, significantly reduced survival, and severe lung injury as shown by hemorrhage, perivascular and lymphatic edema, loss of bronchiolar and alveolar epithelia, severe epithelial cell necrosis, thickened alveoli, extensive inflammation and frequent airspace enlargement

• intratracheal treatment with exogenous surfactant protein B improves survival and lung histology in doxycycline-treated mice 4 days after hyperoxia exposure

respiratory system phenotype ( J:87622 )

N	• under normoxic conditions, mice treated with doxycycline from E0 to P25 exhibit normal lung size and morphology and normal pulmonary mechanics relative to control littermates

abnormal lung vasculature morphology ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display loss of alveolar capillary membrane integrity, perivascular edema, and severe vascular cell necrosis relative to control littermates

lung inflammation ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display increased infiltration by polymorphonuclear cells and alveolar macrophages along with an increased production of IL-1beta, IL-6, and MIP-2 relative to control littermates

abnormal pulmonary alveolus epithelial cell morphology ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display widespread alveolar epithelial cell necrosis without apoptosis, hyaline membrane formation, loss of alveolar capillary membrane integrity, and increased inflammation consistent with severe epithelial cell injury

decreased type II pneumocyte number ( J:87622 )

• after exposure to hyperoxia, staining for proSP-C, a selective marker for type II cells, is decreased in doxycycline-treated mice

pulmonary epithelial necrosis ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display widespread alveolar epithelial cell necrosis without apoptosis

• after exposure to hyperoxia, doxycycline-treated mice display extensive epithelial cell necrosis in the bronchiolar epithelium

pulmonary hyaline membrane formation ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display hyaline membrane formation

increased lung elastance ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display significantly increased lung elastance

increased lung tissue damping ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display significantly increased tissue damping

respiratory distress ( J:87622 )

• doxycycline-treated mice develop acute respiratory distress within 72 hrs of hyperoxia, unlike control littermates which develop severe respiratory symptoms after 5 or more days of continued exposure

abnormal respiratory mechanics ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display altered pulmonary mechanics, indicating a decline in pulmonary function

• however, hysteresivity and newtonian resistance remain unaffected

increased airway resistance ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display a significant increase in airway resistance relative to control littermates

decreased lung compliance ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice display reduced lung compliance relative to control littermates

respiratory failure ( J:87622 )

• doxycycline-treated mice exhibit respiratory failure after relatively short periods of hyperoxia

abnormal surfactant secretion ( J:87622 )

• after exposure to hyperoxia, doxycycline-treated mice show significantly increased BALF protein content and reduced alveolar surfactant phospholipid (saturated phosphatidylcholine) pool sizes relative to control littermates

• after exposure to hyperoxia, SP-B is undetectable while SP-A is significantly decreased in alveolar lavage of doxycycline-treated mice