mortality/aging
• 7-8 weeks after adenoviral Cre intranasal administration to 6- to 8-week old mutants, treated animals are euthanized because they show labored breathing and general wasting
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neoplasm
• cellular origins of cancerous are ambiguous aslesions are Clara Cell antigen-negative, but majority of cells express Surfactant protein C as early as 2 weeks after Cre treatment (CCA and SP-C are both markers of alveolar type II pneumocytes)
• 4 weeks after Cre treatment, mice are treated for 28 days with a pharmacological inhibitor of MEK1/2 which prevents almost all tumor development, while vehicle-treated animals show numerous lung tumors
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• 7 weeks after high dose Cre treatment, evidence of multiple adenomatous tumor formation is present in mouse lungs, while no tumors are detected in untreated mice after 6 months
• papillary adenomas are detected 6-8 weeks after lower dose adenoviral Cre treatment; lesions seem to increase in size and number
• lesions arise in alveolar ducts expanding outward and around broncioles
• at ~14 weeks, papillary adenomas undergo changes at periphery; cells change such that they have more cytoplasm and become eosinophilic
• after lower dose Cre treatement, adenomas do not grow beyond ~900 um in diameter
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• only 2 mice (of 57) that develop adenomas show evidence of progression to adenocarcinoma; cells from these mice display nuclear enlargement, hyperchromasia, and contour irregularities
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respiratory system
• cellular origins of cancerous are ambiguous aslesions are Clara Cell antigen-negative, but majority of cells express Surfactant protein C as early as 2 weeks after Cre treatment (CCA and SP-C are both markers of alveolar type II pneumocytes)
• 4 weeks after Cre treatment, mice are treated for 28 days with a pharmacological inhibitor of MEK1/2 which prevents almost all tumor development, while vehicle-treated animals show numerous lung tumors
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• 7 weeks after high dose Cre treatment, evidence of multiple adenomatous tumor formation is present in mouse lungs, while no tumors are detected in untreated mice after 6 months
• papillary adenomas are detected 6-8 weeks after lower dose adenoviral Cre treatment; lesions seem to increase in size and number
• lesions arise in alveolar ducts expanding outward and around broncioles
• at ~14 weeks, papillary adenomas undergo changes at periphery; cells change such that they have more cytoplasm and become eosinophilic
• after lower dose Cre treatement, adenomas do not grow beyond ~900 um in diameter
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• only 2 mice (of 57) that develop adenomas show evidence of progression to adenocarcinoma; cells from these mice display nuclear enlargement, hyperchromasia, and contour irregularities
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• 4 weeks after Cre administration, lung epithelium hyperplasia is observed
• at earlier times after Cre treatment, hyperplastic epithelium shows papillary outgrowths, but these were not seen at earlier time points (2-4 weeks post-treatment)
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