mortality/aging
• a few homozygotes survive to 4 days of life
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• although homozygotes are present at normal Mendelian ratios throughout fetal development, including E17.5-18.5, fewer than expected homozygotes are born (16% vs expected 25%)
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• most newborn homozygotes die within a few hrs after birth
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vision/eye
• at E18.5, homozygous mutant fetuses display absence of eyelid fusion
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• newborn homozygotes have open eyes
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homeostasis/metabolism
• most homozygotes are born cyanotic and die within a few hrs of birth despite adequate chest movements
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cardiovascular system
• at E18.5, homozygotes display incomplete septation of the single cardiac outflow tract into the aorta and the pulmonary artery
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• at E18.5, homozygotes exhibit persistent truncus arteriosus
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• at E18.5, homozygotes display incomplete formation of the interventricular septum
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liver/biliary system
N |
• homozygotes exhibit normal liver architecture throughout embryonic development and at birth
• in vitro, fetal hepatoblasts derived from E12.5 mutant livers display normal rates of proliferation and apoptosis relative to wild-type fetal hepatoblasts
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cellular
• unlike primary MEFs isolated from E12.5 Juntm1Wag homozygotes that show a proliferation defect due to impaired cell-cycle progression and undergo premature senescence in vitro, MEFs from Juntm1(Junb)Wag homozygotes do not enter premature senescence and show increased proliferation relative to Juntm1Wag cells, but do not proliferate as fast as wild-type cells
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