Analysis Tools
mortality/aging
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• all homozygotes die within 20 minutes after Caesarian birth due to hypoventilation
• however, no external abnormalities or gross pathological defects are detected in placenta or in major organs
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respiratory system
| N |
• at E18.5, mutant feruses display normal pulmonary surfactant production and normal type II pneumocyte morphology, as determined by [3H]acetate incorporation into phospholipids of lung tissue explants, immunostaining of lung tissue for surfactant protein A, B, and C, and EM examination of alveolar cells
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• electrophysiological studies of the brainstem pre-Btzinger respiratory control center indicate an abnormal rhythm discharge with periods of central apnea
• diaphragm electromyography recordings from in vitro preparations isolated from E18.5 mutant fetuses indicate 3-8 apneic episodes of 15-60-sec duration per a 10-min period
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• prior to death, newborn homozygotes exhibit irregular gasps of breath
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• newborn homozygotes exhibit lethal hypoventilation as a result of central apnea and abnormal respiratory rhythmogenesis within the brainstem pre-Btzinger respiratory control center
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nervous system
| N |
• at E18.5, mutant fetuses display no histologic lesions in the nervous system
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• electrophysiological studies of the brainstem pre-Btzinger respiratory control center indicate an abnormal rhythm discharge with periods of central apnea
• diaphragm electromyography recordings from in vitro preparations isolated from E18.5 mutant fetuses show highly irregular respiratory rhythmic patterns with several defining features, including:
• 3-8 apneic episodes of 15-60-sec duration per a 10-min period
• periods of suppressed respiratory rhythmic discharge interspersed with bouts of rhythmic respiratory bursting of significantly higher frequency than observed in wild-type preparations
• augmented breaths of larger amplitude and slightly longer duration
• decreased duration and amplitude of inspiratory bursts (other than augmented bursts)
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homeostasis/metabolism
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• at E10.5, E14.5, and E18.5, homozygotes display a 77%, 64%, and 84% reduction, respectively, in total body myo-inositol levels relative to wild-type littermates
• at E18.5, homozygotes show a 92% reduction in brain inositol levels relative to wild-type littermates (0.60 +/- 0.40 versus 7.80 +/- 0.80 umol/grams of wet weight, respectively)
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• all homozygotes become motionless and cyanotic within 20 min after Caesarian birth
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• at E18.5, homozygotes show a 59% reduction in amniotic fluid inositol levels relative to wild-type littermates (198 uM versus 480 uM, respectively)
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