Phenotypes associated with this allele

• Allele Symbol: Sftpc^tm1Mfbs
• Allele Name: targeted mutation 1, Michael F Beers
• Allele ID: MGI:6360467
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sftpc^tm1Mfbs/Sftpc^tm1Mfbs	B6.Cg-Sftpc^tm1Mfbs	MGI:6740359
cn2	Sftpc^tm1Mfbs/Sftpc^tm1Mfbs Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj/Gt(ROSA)26Sor^+	B6.Cg-Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj Sftpc^tm1Mfbs	MGI:8407106
cn3	Sftpc^tm1Mfbs/Sftpc^+ Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj/Gt(ROSA)26Sor^+	B6.Cg-Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj Sftpc^tm1Mfbs	MGI:8407107

Genotype
MGI:6740359

hm1

• Allelic Composition: Sftpc^tm1Mfbs/Sftpc^tm1Mfbs
• Genetic Background: B6.Cg-Sftpc^tm1Mfbs

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

respiratory system

lung inflammation ( J:267027 )

• age-dependent increase in bronchoalveolar lavage fluid cellularity

abnormal lung morphology ( J:267027 )

• mice develop diffuse parenchymal lung remodeling marked by thickening of alveolar septae beginning at approximately 16 weeks

increased type II pneumocyte number ( J:267027 )

• lungs show an increase in septal cellularity consistent with alveolar type 2 cell hyperplasia at both 16 and 32 weeks of age

thick pulmonary interalveolar septum ( J:267027 )

pulmonary fibrosis ( J:267027 )

• mice show fibrotic remodeling as indicated by an elevation in total lung collagen

immune system

lung inflammation ( J:267027 )

• age-dependent increase in bronchoalveolar lavage fluid cellularity

homeostasis/metabolism

abnormal autophagy ( J:267027 )

• alveolar type 2 cells develop ultrastructural abnormalities consistent with an acquired defect in macroautophagy; hypertrophic alveolar type 2 cells contain numerous intracytoplasmic inclusions composed of proteinaceous debris and mitochondria within double membrane vesicles indicating a late block in macroautophagy

cellular

abnormal autophagy ( J:267027 )

• alveolar type 2 cells develop ultrastructural abnormalities consistent with an acquired defect in macroautophagy; hypertrophic alveolar type 2 cells contain numerous intracytoplasmic inclusions composed of proteinaceous debris and mitochondria within double membrane vesicles indicating a late block in macroautophagy

Genotype
MGI:8407106

cn2

• Allelic Composition: Sftpc^tm1Mfbs/Sftpc^tm1Mfbs; Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}/Gt(ROSA)26Sor⁺
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj} Sftpc^tm1Mfbs

mortality/aging

decreased survivor rate ( J:267027 )

• 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

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

respiratory system

lung inflammation ( J:267027 )

• 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

abnormal lung morphology ( J:267027 )

• 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

increased type II pneumocyte number ( J:267027 )

• 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

pulmonary fibrosis ( J:267027 )

• 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

decreased lung compliance ( J:267027 )

• 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

lung inflammation ( J:267027 )

• 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

abnormal autophagy ( J:267027 )

• 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

hypoxemia ( J:267027 )

• mice exhibit hypoxemia after tamoxifen treatment

cellular

abnormal autophagy ( J:267027 )

• 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

Genotype
MGI:8407107

cn3

• Allelic Composition: Sftpc^tm1Mfbs/Sftpc⁺; Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}/Gt(ROSA)26Sor⁺
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj} Sftpc^tm1Mfbs

respiratory system

alveolitis ( J:267027 )

• adult mice administered intraperitoneal tamoxifen develop moderate alveolitis and interstitial histological changes 2 weeks after induction

immune system

alveolitis ( J:267027 )

• adult mice administered intraperitoneal tamoxifen develop moderate alveolitis and interstitial histological changes 2 weeks after induction

mortality/aging

mortality/aging ( J:267027 )

N • tamoxifen-treated mice do not show early mortality

growth/size/body

growth/size/body region phenotype ( J:267027 )

N • tamoxifen-treated mice do not show weight loss