mortality/aging
• although born in Mendelian ratios, most mice exposed to doxycycline from conception die of respiratory failure at birth
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respiratory system
• doxycycline-exposed newborn mice show a reduction of airspace, sometimes obliterating the alveolar structure
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• doxycycline-exposed newborn mice display increased numbers of Ki-67-positive alveolar cells, indicating increased alveolar cell proliferation
• in addition, neonatal alveolar cells show significantly decreased numbers of TUNEL-positive cells, indicating reduced apoptosis
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• doxycycline-exposed newborn mice lack type I alveolar cells
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• alveoli of doxycycline-exposed newborn mice are lined by immature cuboidal type II cells with a clear cytosol, round nuclei and high glycogen content, indicating a type II cell differentiation arrest
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• immature type II alveolar cells of doxycycline-exposed newborn mice lack lamellar bodies
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• doxycycline-exposed newborn mice lack mature type II alveolar cells
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• doxycycline-exposed newborn mice display thicker alveolar walls due to marked cellular accumulation
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• 86% of mice exposed to doxycycline from conception show signs of respiratory distress within hours after birth
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• most mice exposed to doxycycline from conception to birth display respiratory failure
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• doxycycline-exposed newborn mice show a marked loss of surfactant protein B (SP-B) by immunostaining
• mRNAs for SP-A and SP-D are significantly down-regulated
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liver/biliary system
N |
• doxycycline-exposed mice have a normal liver architecture and show normal Cebpa mRNA levels in liver
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hematopoietic system
N |
• doxycycline-exposed mice exhibit normal granulocytic differentiation in fetal liver and contain granulocytes in peripheral blood
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