Phenotypes Associated with This Genotype

Genotype
MGI:2663596

• Allelic Composition: Epas1^tm1Pec/Epas1^tm1Pec
• Genetic Background: involves: 129/Sv * Swiss

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

mortality/aging

neonatal lethality, complete penetrance ( J:77480 , J:83549 )

• 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)

embryonic lethality during organogenesis, incomplete penetrance ( J:77480 )

• at E13.5, half of mutant embryos die of cardiac failure

prenatal lethality, incomplete penetrance ( J:83549 )

• half of homozygous mutant embryos die during gestation

homeostasis/metabolism

cyanosis ( J:77480 )

• newborn homozygotes display cyanosis

respiratory system

abnormal lung vasculature morphology ( J:77480 )

• 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

abnormal lung development ( J:77480 )

• 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

abnormal pulmonary alveolus epithelial cell morphology ( J:77480 )

• 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

abnormal alveolar lamellar body morphology ( J:77480 )

• 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

decreased type II pneumocyte number ( J:77480 )

• 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

atelectasis ( J:77480 )

• lung aeration (percentage of total surface filled with air) fails to increase after birth

thick pulmonary interalveolar septum ( J:77480 )

• a significantly increased alveolar septal thickness is noted at E18.5 and at birth

respiratory distress ( J:77480 )

• 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

respiratory failure ( J:77480 )

• newborn homozygotes display severe respiratory failure due to extensive lung collapse

abnormal surfactant secretion ( J:77480 )

• newborn homozygotes produce less surfactant phospholipids and less SP-A, SP-B and SP-D than wild-type controls

cardiovascular system

abnormal lung vasculature morphology ( J:77480 )

• 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

abnormal angiogenesis ( J:77480 )

• at E18.5, pulmonary angiogenesis is impaired as capillaries in the saccular septa fail to remodel properly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
newborn respiratory distress syndrome		DOID:12716	OMIM:267450	J:77480