Phenotypes Associated with This Genotype

Genotype
MGI:5644303

• Allelic Composition: Tg(SFTPC-Tnf)2Pva/0
• Genetic Background: involves: C57BL/6 * DBA/2

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

mortality/aging

premature death ( J:28120 )

• mice die from pulmonary disease, with death ranging from within a few weeks from birth to progression through over 6 months

respiratory system

lung hemorrhage ( J:28120 )

• microhemorrhages in the lung

alveolitis ( J:28120 )

• mice show varying degrees of lymphocytic alveolitis

• at 2 months of age, leukocytic alveolitis is more patchy than diffuse, with lymphocytic infiltrates more prominent within the interlobular septa, around the extraalveolar small vessels, and under the pleura, and mostly CD4+ lymphocytes, but also CD8+ and B lymphocytes are seen, with variable numbers of neutrophils

• at 6 months of age, lymphocytic accumulation is seen, sometimes associated with the presence of polymorphonuclear leukocytes and plasma cells

interstitial pneumonia ( J:28120 )

• mice that die at 1 month of age exhibit severe interstitial pneumonia with large areas of pulmonary consolidation

abnormal respiratory system morphology ( J:222067 )

• airways show an increase in collagen and hyaluronan content, and a decrease in elastin content

abnormal lung morphology ( J:28120 )

• lungs have an irregular yellow surface at 6 months of age

abnormal lung vasculature morphology ( J:28120 )

• 2 month old mice show frequent endothelial swelling in the alveolar capillaries

• thickening of the endothelial cytoplasm in the alveolar capillaries at 6 months of age

abnormal pulmonary alveolar system morphology ( J:28120 )

• irregular and large alveolar spaces probably resulting from ruptures of alveolar septa

abnormal pulmonary alveolus epithelium morphology ( J:28120 )

• intraalveolar epithelial desquamation, showing intraalveolar aggregates of foamy cells, sometimes containing cholesterol crystals

• hyperplasia of type II alveolar epithelial cells

abnormal type II pneumocyte morphology ( J:28120 )

• thickened alveolar septa are lined by hyperplastic type II epithelial cells, which appear poor in lamellated bodies and with empty vacuoles, indicating cell damage and rapid regeneration among type II pneumocytes

abnormal pulmonary alveolus wall morphology ( J:222067 )

• alveolar walls show an increase in collagen and hyaluronan content, and a decrease in elastin content

increased pulmonary alveolus wall thickness ( J:28120 )

• thickened alveolar walls

abnormal pulmonary interalveolar septum morphology ( J:28120 )

• ruptures of some alveolar septa are seen at 2 months of age, resulting in an enlargement of the alveolar spaces

thick pulmonary interalveolar septum ( J:28120 )

• thickening of the alveolar septa with remodeling of the air space is seen at 6 months of age

• thickening of septa is due to an increased number of fibroblasts

• thickened alveolar septa are lined by type II epithelial cells

emphysema ( J:222067 )

• mice exhibit pulmonary emphysema, with an enlargement of alveolar spaces

pulmonary fibrosis ( J:28120 , J:222067 )

• minimal fibrosis is seen at 2 months, however, by 6 months of age, marked fibrosis of alveolar spaces is seen, with extensive collagen fibrils accumulation (J:28120)

respiratory distress ( J:28120 )

respiratory failure ( J:28120 )

• progressive respiratory failure by 7 months of age

cardiovascular system

abnormal lung vasculature morphology ( J:28120 )

• 2 month old mice show frequent endothelial swelling in the alveolar capillaries

• thickening of the endothelial cytoplasm in the alveolar capillaries at 6 months of age

lung hemorrhage ( J:28120 )

• microhemorrhages in the lung

hematopoietic system

abnormal platelet cell number ( J:28120 )

• platelets lining the alveolar capillary endothelium and platelet clumps are seen with unusual frequency

homeostasis/metabolism

abnormal blood coagulation ( J:28120 )

• an increase in platelet trapping in the lungs

cyanosis ( J:28120 )

increased hyaluronic acid level ( J:222067 )

• airways and alveolar walls show an increase in hyaluronan content

increased collagen level ( J:222067 )

• airway and alveolar wall collagen content is increased, with deposition of collagens in the pleura, perivascular, and peribronchiolar in the basement membrane and connective tissue and in the alveolar walls

immune system

alveolitis ( J:28120 )

• mice show varying degrees of lymphocytic alveolitis

• at 2 months of age, leukocytic alveolitis is more patchy than diffuse, with lymphocytic infiltrates more prominent within the interlobular septa, around the extraalveolar small vessels, and under the pleura, and mostly CD4+ lymphocytes, but also CD8+ and B lymphocytes are seen, with variable numbers of neutrophils

• at 6 months of age, lymphocytic accumulation is seen, sometimes associated with the presence of polymorphonuclear leukocytes and plasma cells

interstitial pneumonia ( J:28120 )

• mice that die at 1 month of age exhibit severe interstitial pneumonia with large areas of pulmonary consolidation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
idiopathic pulmonary fibrosis		DOID:0050156		J:28120