Analysis Tools
mortality/aging
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• no homozygotes survive beyond 6 weeks of age
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• about 30% of homozygotes die early postnatally
• homozygotes surviving P4 live for an average of 3-4 weeks
• however, no homozygotes survive beyond 6 weeks of age
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• about 50% of homozygotes die before E10, with no subsequent loss during the prenatal period
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growth/size/body
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• at >2 weeks, homozygotes exhibit right ventricular hypertrophy, probably as a result of pulmonary dysfunction ("cor pulmonale")
• no cardiac dysmorphology is noted during embryonic or early postnatal stages
• no apparent hemorrhaging, anemia, erythroblastosis or thrombocytopenia are observed
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• postnatal survivors exhibit an enlarged thoracic cavity, with lungs appearing to expand until tissue breaks
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• by 4 weeks, surviving homozygotes are at least 50% smaller than wild-type mice
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• at >2 weeks, homozygotes show a symmetrical size reduction in most organs
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• at E17-E19, surviving homozygotes are 10-20% smaller than wild-type fetuses
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• at E17-E19, surviving homozygotes are growth retarded
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respiratory system
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• postmortem, several homozygotes exhibit bleeding in the lungs
• bleeding and pneumothorax are two potential causes of postnatal lethality
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• at >2 weeks, mutant lungs appear hyperinflated, with abnormally large, air-filled cavities throughout the parenchyma
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• at P10-P14, homozygotes display failure of alveolar septation
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• at >2 weeks, pulmonary alveoli are absent
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atelectasis
(
J:33629
)
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• at P14, mutant lungs show large areas of atelectasis; smaller areas of collapsed lung tissue are evident as early as P4
• by P19, atelectasis often affects entire lung lobes, resulting in distension of the remaining air-filled lobes
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• at >2 weeks, alveolar septa are absent
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• little subcompartmentalization of lung parenchyma occurs after P4
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• at 3 weeks, mutant lungs show loss of alveolar myofibroblasts and parenchymal elastin, with a "clear zone" extending into the narrow space between the type I pneumocyte and capillary endothelial cell cytoplasm
• loss of septal myofibrils and elastin fibers is specific to lung parenchyma, as elastin fibers occur at normal abundance in blood vessel and bonchus walls
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pneumothorax
(
J:33629
)
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• upon autopsy and during dissections under phosphate-buffered saline, air bubbles were frequently observed to leave the pleural surfaces of mutant lungs
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cardiovascular system
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• at >2 weeks, homozygotes exhibit right ventricular hypertrophy, probably as a result of pulmonary dysfunction ("cor pulmonale")
• no cardiac dysmorphology is noted during embryonic or early postnatal stages
• no apparent hemorrhaging, anemia, erythroblastosis or thrombocytopenia are observed
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• at >2 weeks, homozygotes show a >2-fold increase in right ventricular wall thickness relative to heterozygotes
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• postmortem, several homozygotes exhibit bleeding in the lungs
• bleeding and pneumothorax are two potential causes of postnatal lethality
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muscle
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• at >2 weeks, homozygotes exhibit right ventricular hypertrophy, probably as a result of pulmonary dysfunction ("cor pulmonale")
• no cardiac dysmorphology is noted during embryonic or early postnatal stages
• no apparent hemorrhaging, anemia, erythroblastosis or thrombocytopenia are observed
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