mortality/aging
• newborn mice exposed to doxycycline from E6.5 develop respiratory distress and die within 1-2 hrs of birth
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respiratory system
• at E18.5, doxycycline-exposed mice display an almost complete absence of pulmonary capillaries associated with defective primary septation during distal lung morphogenesis
• at E18.5, lung saccular walls without capillaries exhibit no septae while septae containing a residual (single) capillary or disorganized capillaries are malformed and show abnormal shapes with an expanded mesenchyme
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• at E18.5, doxycycline-exposed mice exhibit significantly reduced pulmonary endothelial cell development relative to controls
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• at birth, doxycycline-exposed mice display white lungs, indicating a lack of pulmonary circulation
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• mice exposed to doxycycline from E6.5 display defective distal lung saccular development due to reduced primary septation; first seen at E16.5 when terminal tubules appear more dilated
• defective distal airspace morphogenesis is also noted when mice are exposed to doxycycline from E14.5 to birth
• impaired primary septation is likely due to reduced hepatocyte growth factor (Hgf) expression
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• at E18.5, doxycycline-exposed mice display a significant reduction in proliferating (BrdU+) lung mesenchymal cells relative to controls
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• at E18.5, doxycycline-exposed mice display significantly dilated distal airspaces with fewer subdivisions by primary septae than controls
• at E18.5, doxycycline-exposed mice display a mosaic pattern of normal and abnormal septae that is dependent on the residual capillary structures
• at birth, ventilation of doxycycline-exposed lungs results in marked dilation of terminal airspaces and thinning of saccular walls
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• at E18.5, doxycycline-exposed mice display a 65% reduction in proliferating (BrdU+) lung epithelial cells relative to controls
• however, epithelial cell survival and proximal-distal patterning of epithelial cell differentiation remain normal
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• at E16.5 and E17.5, doxycycline-exposed mice display abnormal distal acini and more dilated distal tubules than controls
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• newborn mice exposed to doxycycline from E6.5 develop respiratory distress and die within 1-2 hrs of birth
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cardiovascular system
• at E18.5, doxycycline-exposed mice display an almost complete absence of pulmonary capillaries associated with defective primary septation during distal lung morphogenesis
• at E18.5, lung saccular walls without capillaries exhibit no septae while septae containing a residual (single) capillary or disorganized capillaries are malformed and show abnormal shapes with an expanded mesenchyme
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• at E18.5, doxycycline-exposed mice exhibit significantly reduced pulmonary endothelial cell development relative to controls
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• at E18.5, doxycycline-exposed mice display significantly reduced pulmonary capillary angiogenesis associated with defective primary septation during distal lung morphogenesis
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• at birth, doxycycline-exposed mice display white lungs, indicating a lack of pulmonary circulation
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cellular
• at E18.5, doxycycline-exposed mice display a significant reduction in proliferating (BrdU+) lung mesenchymal cells relative to controls
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