Mouse Genome Informatics
involves: 129P2/OlaHsd
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
• homozygotes die within 12-48 hours after birth
• administration of indomethacin, which inhibits PGE2 production, rescues neonatal lethality and ductus arteriosus patency

cardiovascular system
• newborn homozygotes fail to exhibit remodeling of the ductus arteriosus i.e. lifting of endothelial cells, fragmentation of elastic lamina, migration of smooth-muscle cells and obstruction of lumen by intimal thickening
• newborn homozygotes exhibit a patent ductus arteriosus of a similar diameter to that of a full-term fetus
• newborn homozygotes die of congestive heart failure as a result of left-ventricle overload and exposure of the right ventricle to arterial pressures

• newborn homozygotes exhibit significantly increased PGE2 levels; in contrast, TxB2 levels remain normal
• perinatal PGE2 levels remain abnormally elevated, intracellular cAMP levels do not change, and DA remodeling is inhibited

Mouse Models of Human Disease
Patent Ductus Arteriosus 607411 J:74466