Mouse Genome Informatics
hm
    Epas1tm1Pec/Epas1tm1Pec
involves: 129/Sv * Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 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)
• at E13.5, half of mutant embryos die of cardiac failure
• half of homozygous mutant embryos die during gestation

homeostasis/metabolism
• newborn homozygotes display cyanosis

respiratory system
• 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 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
• however, no differences in epithelial cell proliferation or apoptosis are observed
• epithelial cell differentiation is impaired; abundant immature PAS+ (glycogen-rich) epithelial cells are shown to persist after E18.5, unlike in wild-type lungs
• 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
• 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
• a significantly increased alveolar septal thickness is noted at E18.5 and at birth
• 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
• newborn homozygotes display severe respiratory failure due to extensive lung collapse
• newborn homozygotes produce less surfactant phospholipids and less SP-A, SP-B and SP-D than wild-type controls
• lung aeration (percentage of total surface filled with air) fails to increase after birth

cardiovascular system
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Respiratory Distress Syndrome in Premature Infants 267450 J:77480