mortality/aging
• homozygotes are alive at the expected Mendelian ratio up to E18.5; however, no viable homozygotes are recovered at P1
• after Caesarean section at E18.5, all homozygous mutant neonates die within 15 min
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nervous system
• at E12.5, homozygotes exhibit severe neuronal apoptosis in the developing nervous system, with extensive TUNEL-positive and pyknotic cells in the cortex, hindbrain and dorsal root ganglion; in contrast, neither TUNEL-positive nor pyknotic cells are detected in the lungs or liver
• neuronal apoptosis occurs in newly generated post-mitotic neuronal cells and is closely associated with the period between onset and cessation of neurogenesis
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• mutant embryos display defective neurogenesis characterized by increased neuronal apoptosis first evident in the dorsolateral region of the cortex at E12.5, after the onset of neurogenesis
• extensive neuronal cell death is still noted at E14.5 but decreases gradually thereafter and disappears almost completely at E18.5
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• at E16.5 and E18.5, the mutant dorsolateral cortex is composed of a thin cortical plate as a result of extensive cell death
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respiratory system
• in mutant lungs, alveolar air spaces are reduced
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atelectasis
(
J:61143
)
• lungs of mutant neonates fail to inflate with air
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• all homozygotes die of a respiratory failure immediately after birth
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growth/size/body
• all homozygous mutant embryos exhibit growth retardation throughout stages E10.5-E18.5, with an ~30% decrease in body weight after E13.5
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homeostasis/metabolism
behavior/neurological
• all mutant neonates respond to pain stimulus when their tails are pinched with forceps, but they rapidly lose the reflex action within 15 min after Caesarian section
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embryo
• all homozygous mutant embryos exhibit growth retardation throughout stages E10.5-E18.5, with an ~30% decrease in body weight after E13.5
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integument
cellular
• at E12.5, homozygotes exhibit severe neuronal apoptosis in the developing nervous system, with extensive TUNEL-positive and pyknotic cells in the cortex, hindbrain and dorsal root ganglion; in contrast, neither TUNEL-positive nor pyknotic cells are detected in the lungs or liver
• neuronal apoptosis occurs in newly generated post-mitotic neuronal cells and is closely associated with the period between onset and cessation of neurogenesis
|
• mutant embryos display defective neurogenesis characterized by increased neuronal apoptosis first evident in the dorsolateral region of the cortex at E12.5, after the onset of neurogenesis
• extensive neuronal cell death is still noted at E14.5 but decreases gradually thereafter and disappears almost completely at E18.5
|