Analysis Tools
mortality/aging
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• newborn homozygotes die within 2-3 hours of life due to severe respiratory failure
(J:77480)
• homozygous mutants surviving embryogenesis die at birth
(J:83549)
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• at E13.5, half of mutant embryos die of cardiac failure
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• half of homozygous mutant embryos die during gestation
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homeostasis/metabolism
respiratory system
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• at E18.5, a small deficit in vascularization of saccular septa is observed, as determined by the number of vessels/sacculus
• unlike in newborn wild-type mice where capillaries are juxtaposed to the lumen in ~95% of terminal sacs, mutant capillaries lay more distant from the lumen in ~30% of terminal sacs
• however, basement membrane formation of microvessels in the septa is normal and branching of large pulmonary vessels is unaffected
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• at birth, thinning of the alveolar septa is impaired due to defective epithelial differentiation
• unlike in wild-type lungs, immature PAS+ (glycogen-rich) epithelial cells fail to progressively disappear after E18.5
• at >E16.5, pulmonary VEGF protein levels increased by ~4-fold in wild-type
fetuses, but only minimally in mutant fetuses
• in mutant neonates, pulmonary VEGF transcript levels are reduced by ~30% in type II pneumocytes
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• epithelial cell differentiation is impaired; abundant immature PAS+ (glycogen-rich) epithelial cells are shown to persist after E18.5, unlike in wild-type lungs
• however, no differences in epithelial cell proliferation or apoptosis are observed
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• lamellar bodies persist in the alveolar lumen and fail to form myelin structures and a surfactant layer, unlike in wild-type lungs where surfactant lamellar bodies are found inside type II pneumocytes
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• in newborn homozygotes, the number of surfactant protein-B (SP-B) and SP-D positive type II pneumocytes is decreased relative to that in wild-type controls
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atelectasis
(
J:77480
)
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• lung aeration (percentage of total surface filled with air) fails to increase after birth
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• a significantly increased alveolar septal thickness is noted at E18.5 and at birth
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• newborn homozygotes breath irregularly and display gasping and signs of retraction
• not due to growth retardation, respiratory muscle dysfunction, lung hypoplasia, impaired fluid clearance, hypoxic stress or other organ defects
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• newborn homozygotes display severe respiratory failure due to extensive lung collapse
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• newborn homozygotes produce less surfactant phospholipids and less SP-A, SP-B and SP-D than wild-type controls
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cardiovascular system
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• at E18.5, a small deficit in vascularization of saccular septa is observed, as determined by the number of vessels/sacculus
• unlike in newborn wild-type mice where capillaries are juxtaposed to the lumen in ~95% of terminal sacs, mutant capillaries lay more distant from the lumen in ~30% of terminal sacs
• however, basement membrane formation of microvessels in the septa is normal and branching of large pulmonary vessels is unaffected
|
|
• at E18.5, pulmonary angiogenesis is impaired as capillaries in the saccular septa fail to remodel properly
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| newborn respiratory distress syndrome | DOID:12716 |
OMIM:267450 |
J:77480 | |
