Analysis Tools
mortality/aging
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• tamoxifen-treated mice show decreased survival, with onset of mortality as early as 5 days after induction
• mean survival is lower in males (10.6 days vs. 11.9 days) than in females following tamoxifen treatment
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growth/size/body
weight loss
(
J:267027
)
|
• tamoxifen-treated mice exhibit increased weight loss
• tamoxifen-treated mice surviving the acute injury phase show partial recovery from the nadir in body weight
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respiratory system
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• bilateral pulmonary infiltrates appear, accompanied by increases in BALF protein, peaking at days 7-14 after tamoxifen induction
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alveolitis
(
J:267027
)
|
• tamoxifen-treated mice show onset of complex, multiphasic alveolitis
• bronchoalveolar lavage fluid (BALF) from tamoxifen-treated mice shows increases in total cell counts beginning by day 8 and peaking 2 weeks after induction
• BALF shows a complex inflammatory cell prolife after tamoxifen induction, with an early and sustained macrophage accumulation beginning at 7 days, a spike in polymorphonuclear cells (on day 7), and transient alveolar eosinophilia (peak at 2 weeks), and an increase in total lymphocytes by day 7, indicating polycellular alveolitis and diffuse parenchymal damage
|
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• tamoxifen-treated mice develop acute, diffuse lung injury, with time-dependent progression from patchy peribronchial cell infiltrates and interstitial expansion (7 days) to frank parenchymal injury (2 weeks)
• tamoxifen-treated mice show heterogenous parenchymal remodeling with mesenchymal accumulation of alpha-smooth muscle actin-positive cells adjacent to dilated airspaces lined by hyperplastic alveolar type 2 cells at 4-6 weeks after induction
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• lungs show a 40% persistent increase in alveolar type 2 cell numbers beginning at 7 days after tamoxifen treatment
• however, no significant apoptosis of alveolar type 2 cells is seen after tamoxifen treatment
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• tamoxifen-treated mice surviving the acute lung injury phase develop a fibrotic histological phenotype indicating spontaneous fibrotic lung remodeling
• mice show increased collagen deposition in peripheral lung parenchyma and subpleural regions beginning at 2 weeks after tamoxifen-induction
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• pressure-volume curves at 4 and 6 weeks following tamoxifen treatment are shifted down (decreased volume with increased pressure) and to the right, with reduced static compliance, indicating restrictive lung physiology
• static compliance, maximally decreased at 4 weeks by 40%, mildly improves at week 6 after tamoxifen-treatment
|
immune system
|
• bilateral pulmonary infiltrates appear, accompanied by increases in BALF protein, peaking at days 7-14 after tamoxifen induction
|
alveolitis
(
J:267027
)
|
• tamoxifen-treated mice show onset of complex, multiphasic alveolitis
• bronchoalveolar lavage fluid (BALF) from tamoxifen-treated mice shows increases in total cell counts beginning by day 8 and peaking 2 weeks after induction
• BALF shows a complex inflammatory cell prolife after tamoxifen induction, with an early and sustained macrophage accumulation beginning at 7 days, a spike in polymorphonuclear cells (on day 7), and transient alveolar eosinophilia (peak at 2 weeks), and an increase in total lymphocytes by day 7, indicating polycellular alveolitis and diffuse parenchymal damage
|
homeostasis/metabolism
|
• alveolar type II cell lysates from adult mice administered intraperitoneal tamoxifen show an increase in both LC3-II and p62, indicating a late block in macroautophagy, as early as 1 week after tamoxifen induction
|
cellular
|
• alveolar type II cell lysates from adult mice administered intraperitoneal tamoxifen show an increase in both LC3-II and p62, indicating a late block in macroautophagy, as early as 1 week after tamoxifen induction
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| idiopathic pulmonary fibrosis | DOID:0050156 | J:267027 | ||
