mortality/aging
• mice die from pulmonary disease, with death ranging from within a few weeks from birth to progression through over 6 months
|
respiratory system
• 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
|
• mice that die at 1 month of age exhibit severe interstitial pneumonia with large areas of pulmonary consolidation
|
• airways show an increase in collagen and hyaluronan content, and a decrease in elastin content
|
• lungs have an irregular yellow surface at 6 months of age
|
• 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
|
• irregular and large alveolar spaces probably resulting from ruptures of alveolar septa
|
• intraalveolar epithelial desquamation, showing intraalveolar aggregates of foamy cells, sometimes containing cholesterol crystals
• hyperplasia of type II alveolar epithelial cells
|
• 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
|
• alveolar walls show an increase in collagen and hyaluronan content, and a decrease in elastin content
|
• thickened alveolar walls
|
• ruptures of some alveolar septa are seen at 2 months of age, resulting in an enlargement of the alveolar spaces
|
• 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
|
• 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)
|
• progressive respiratory failure by 7 months of age
|
cardiovascular system
• thickening of the endothelial cytoplasm in the alveolar capillaries at 6 months of age
• 2 month old mice show frequent endothelial swelling in the alveolar capillaries
|
• microhemorrhages in the lung
|
hematopoietic system
• platelets lining the alveolar capillary endothelium and platelet clumps are seen with unusual frequency
|
homeostasis/metabolism
• an increase in platelet trapping in the lungs
|
• airways and alveolar walls show an increase in hyaluronan content
|
• 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
|
• 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 |