All Phenotypes Sftpc<tm2Mfbs> MGI Mouse

premature death ( J:279196 )

• mice exhibit tamoxifen dose-dependent morbidity and mortality

• at a dose of 350 mg/kg tamoxifen, mice show 40% early mortality at 14 days after treatment

• at a high dose of 600 mg/kg tamoxifen, mice show 100% lethality before 14 days after treatment

• lower doses of tamoxifen are nonfatal

weight loss ( J:279196 )

• at a dose of 350 mg/kg tamoxifen, mice develop weight loss starting 7 days after treatment

increased lung apoptosis ( J:279196 )

• lungs show an increase in apoptosis at 7 days after tamoxifen treatment

alveolitis ( J:279196 )

• parenchymal lung injury in tamoxifen-treated mice is accompanied by polycellular alveolitis, with an increase in total bronchoalveolar lavage fluid (BALF) cell counts beginning 7 days after tamoxifen treatment and peaking at 2 weeks

• BALF shows an early and sustained increase in macrophage/monocyte lineages beginning 7 days after tamoxifen, a raise in neutrophils starting 7 days after tamoxifen and peaking by 2 weeks, and an increase in eosinophils at 2 weeks, indicating granulocyte alveolitis, and an increase in total lymphocytes increased by day 14 and sustained through 28 days

• tamoxifen-treated mice show an early decrease in the relative percentage of SigF+CD11b- resident alveolar macrophages commensurate with an influx of inflammatory CD11b+Ly6C+ monocytes at 3 days after treatment

abnormal lung morphology ( J:279196 )

• tamoxifen-treated mice develop acute, diffuse lung injury by day 14

decreased type II pneumocyte number ( J:279196 )

• lungs show a decline in alveolar type 2 cell number from 1 week after tamoxifen treatment, with heterogeneous regions of higher and lower alveolar type 2 cell density

pulmonary fibrosis ( J:279196 )

• 4 weeks after tamoxifen treatment, lungs show heterogeneous areas of dense trichrome-positive parenchymal remodeling in association with the accumulation of smooth muscle actin-positive cells adjacent to hyperplastic alveolar type 2 cells and an increase in lung collagen deposition, indicating development of spontaneous fibrotic lung remodeling

decreased lung compliance ( J:279196 )

• mice show restrictive impairment on lung mechanics 4 weeks after tamoxifen treatment, with flow volume curves showing a 30% decline in static lung compliance

increased cytokine level ( J:279196 )

• BALF at early-state alveolitis exhibits increased CCL2, CCL17, and CCL7 levels

• BALF shows an increase in eosinophil chemokines CCL11 and IL-5 at 1 week after tamoxifen treatment, however no increase in the Th2 cytokines IL-4 and IL-13 is seen

• BALF shows an increase in IL-6 and a 10-fold increase in CXCL1 at 1 week after tamoxifen

• alveolar type 2 cells show increased Ccl2, Ccl17, Ccl7, Ccl11, Il-5, CXCL1 mRNA levels at 1 week after tamoxifen, but not Il-6 mRNA levels, suggesting that alveolar type 2 cells are an early source of all these cytokines except for IL-6

alveolitis ( J:279196 )

• parenchymal lung injury in tamoxifen-treated mice is accompanied by polycellular alveolitis, with an increase in total bronchoalveolar lavage fluid (BALF) cell counts beginning 7 days after tamoxifen treatment and peaking at 2 weeks

• BALF shows an early and sustained increase in macrophage/monocyte lineages beginning 7 days after tamoxifen, a raise in neutrophils starting 7 days after tamoxifen and peaking by 2 weeks, and an increase in eosinophils at 2 weeks, indicating granulocyte alveolitis, and an increase in total lymphocytes increased by day 14 and sustained through 28 days

• tamoxifen-treated mice show an early decrease in the relative percentage of SigF+CD11b- resident alveolar macrophages commensurate with an influx of inflammatory CD11b+Ly6C+ monocytes at 3 days after treatment

impaired autophagy ( J:279196 )

• alveolar type 2 cells from tamoxifen-injected mice exhibit a block in macroautophagy

hypoxemia ( J:279196 )

• the weight loss and death of tamoxifen-treated mice are commensurate with hypoxemia

increased cytokine level ( J:279196 )

• BALF at early-state alveolitis exhibits increased CCL2, CCL17, and CCL7 levels

• BALF shows an increase in eosinophil chemokines CCL11 and IL-5 at 1 week after tamoxifen treatment, however no increase in the Th2 cytokines IL-4 and IL-13 is seen

• BALF shows an increase in IL-6 and a 10-fold increase in CXCL1 at 1 week after tamoxifen

• alveolar type 2 cells show increased Ccl2, Ccl17, Ccl7, Ccl11, Il-5, CXCL1 mRNA levels at 1 week after tamoxifen, but not Il-6 mRNA levels, suggesting that alveolar type 2 cells are an early source of all these cytokines except for IL-6

increased transforming growth factor beta level ( J:279196 )

• BALF shows an increase in TGF-beta1, with levels peaking at 2 weeks after tamoxifen treatment

impaired autophagy ( J:279196 )

• alveolar type 2 cells from tamoxifen-injected mice exhibit a block in macroautophagy

increased lung apoptosis ( J:279196 )

• lungs show an increase in apoptosis at 7 days after tamoxifen treatment

increased endoplasmic reticulum stress ( J:279196 )

• alveolar type 2 cells exhibit endoplasmic reticulum (ER) stress following tamoxifen treatment

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
interstitial lung disease		DOID:3082	OMIM:PS619611	J:279196

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

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