Analysis Tools
mortality/aging
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• only 1 of 17 pups survived until P28
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• pups failed to thrive and died within 2-3 weeks of life
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growth/size/body
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• at birth, pups appeared grossly normal but were already smaller than control littermates
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• pups failed to thrive and by P21 were much smaller than control littermates
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respiratory system
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• at E11.5, E14.5 and E18.5, mutant lungs showed normal gross morphology and size relative to control lungs
• no defects in the branching pattern were detected when E11.5 lungs were cultured for 24 and 48 hrs
• distal epithelium differentiation (formation of alveolar sacs and type I and type II cells) remained unaffected
• normal formation of goblet cells was observed in the trachea at birth (P0)
• the distribution and number of basal cells remained normal
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• by P21, isolated foci of inflammatory cells, including macrophages, were seen in the bronchiolar epithelium, unlike in control lungs
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• at P7, P14 and P21, a severely attenuated airway epithelium is noted in medium-sized airways and in terminal bronchioles
• at E18.5, the respiratory epithelium was populated almost exclusively by beta-tubulin-expressing ciliated cells, unlike in control lungs where ciliated cells were interspersed with secretory Clara cells
• at E18.5, Foxj1-positive ciliated cells comprised 80-85% of the population of the airway epithelium, regardless of the airway generation, unlike in control lungs where Foxj1-expressing cells averaged 40%, 18% and 17% of epithelial cells seen in the large, medium and small airways, respectively
• at E18.5, Ki67 labeling averaged 15%, 10% and 5% of control values in large, medium and small airways, respectively, suggesting a substantial decrease in epithelial cell proliferation
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• by P21, a thin metaplastic squamous epithelium, scattered cell debris and isolated macrophages were observed instead of the typical cuboidal epithelium seen in control bronchioles
• however, none of these changes were apparent at birth or at E18.5
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• no secretory Clara cells were detected at E18.5 and P0, as determined by specific marker expression analysis
• however, no differences in apoptosis were noted at E14.5, E18.5 and P0 lungs
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immune system
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• by P21, isolated foci of inflammatory cells, including macrophages, were seen in the bronchiolar epithelium, unlike in control lungs
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nervous system
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• at E18.5, the number of neuroendocrine cells is significantly increased in mutant airways, as shown by Pgp9.5
immunostaining
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endocrine/exocrine glands
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• at E18.5, the number of neuroendocrine cells is significantly increased in mutant airways, as shown by Pgp9.5
immunostaining
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