mortality/aging
• 82% of mice treated with doxycycline from E7.5 to E14.5 die within the first 24 hrs after birth due to respiratory failure
|
respiratory system
N |
• mice treated with doxycycline during postnatal period P3-P30 show no differences in overall lung morphology or expression of epithelial marker proteins relative to control littermates
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 display pulmonary congestion
|
• mice treated with doxycycline from E7.5 to E14.5 display delayed lung maturation, as shown by reduced lung sacculation and mesenchymal thickening prior to birth (E17.5 and E18.5)
• however, branching morphogenesis and proliferation of distal respiratory epithelial cells is normal at E15.5 and E18.5
• no vascular abnormalities are detected at E18.5, as shown by normal Pecam-1 staining
• differentiation of ciliated and Clara cells in conducting airways remains normal
|
• mice treated with doxycycline from E7.5 to E14.5 display reduced lung sacculation prior to birth
• consistent with delayed lung maturation, peripheral lung tubules remain closed, unlike in control littermates
|
• mice treated with doxycycline from E7.5 to E14.5 display smaller peripheral saccules at E17.5 and E18.5
|
• increased mesenchymal thickness prior to birth
|
• mice treated with doxycycline from E7.5 to E14.5 show delayed differentiation of type I and type II epithelial cells
|
• mice treated with doxycycline from E7.5 to E14.5 display reduced numbers of squamous type I epithelial cells
• however, type I epithelial cells appear ultrastructurally normal
|
• mice treated with doxycycline from E7.5 to E14.5 show significantly smaller lamellar bodies in type II cells relative to control littermates
|
atelectasis
(
J:142246
)
• mice treated with doxycycline from E7.5 to E14.5 display focal atelectasis
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 display pulmonary congestion, focal atelectasis, bronchial occlusion, and hyaline membranes lining terminal airways consistent with severe respiratory distress syndrome (RDS)
• ~18% of mice treated with doxycycline from E7.5 to E14.5 survive after birth and exhibit mild RDS with focal atelectasis
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 display hyaline membranes lining the terminal airways
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 display severe respiratory distress
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 die within the first 24 hrs after birth due to respiratory failure
|
• mice treated with doxycycline from E7.5 to E14.5 show reduced pulmonary SP-A, SP-B, SP-C, and SP-D mRNA levels at E17.5 relative to control littermates
• SP-B mRNA is reduced to 40% of control values
|
cardiovascular system
• 82% of mice treated with doxycycline from E7.5 to E14.5 display pulmonary congestion
|