mortality/aging
• ~50% of mutants develop normally into adulthood with no obvious lung defects
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• ~50% of mutants die at or shortly after birth with a severe lung phenotype
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respiratory system
• at E18.5 the lungs of affected mutants are composed of numerous large fluid-filled sacs containing cellular debris lined by highly attenuated epithelial cells separated by a thin layer of mesoderm
• however, lung size, lobulation pattern, and trachea morphology are normal
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• at E15.5-E16.5, a reduction in the proportion of proliferating cells in the endoderm is seen
• at E15.5, E16.5 and E18.5, abundant apoptotic cells are detected in the lumen, epithelium and mesenchyme, unlike in wild-type lungs
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• at E14.5-E16.5 in affected mutants, branching is reduced with only a few expanded tubes separated by abundant mesoderm present
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• at E14.5, E15.5 and E18.5, epithelial cell size is irregular, dead cells are seen in the lumen, and increased apoptosis is seen
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• at E18.5, attenuated presumptive type I cells are lining the large sacs
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• at E18.5, a paucity of type II cells is observed in the mutant lung
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