mortality/aging
• only 14.5% of offspring are homozygous, instead of the expected 25%; examination of embryos between E10 and 18.5 reveals cardiac defects first observed at E10 but no time of lethality is provided
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cardiovascular system
• at E10.5, ~35% of homozygous embryos display dilated outflow vessels (aortic and pulmonary arteries)
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• at E10.5, ~35% of homozygous embryos display dilated cardiac atria
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• at E10.5, ~35% of homozygous embryos display dilated cardiac ventricles
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cellular
• mitochondria of myoepithelial cells are swollen and lack normal crystal structures
• mitochondria in some mutant muscle fibers are swollen and exhibit degeneration
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• mitochondria in some mutant muscle fibers are swollen and exhibit degeneration
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homeostasis/metabolism
endocrine/exocrine glands
• at 9 days after parturition, overall abundance of mammary gland tissue is similar, or even increased, in mutants vs wild-type
• at days 9 and 13 postpartum, a progressive loss of epithelial cell components and an increase in adipose tissue is observed
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• premature onset of involution-like process precludes sustained lactation beyond the first week after birth
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• the mutant alveolar epithelium appears flattened in the initial postpartum
period, unlike in wild-type controls
• a progressive loss of epithelial cell components is noted at postpartum days 9 and 13 in mutant mammary glands
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• the lumina of mutant mammary alveoli are full of milk and become dilated in the initial postpartum period (postpartum day 5)
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• loss of the normal reddish-pink color of mammary gland tissue; a light yellow-tan color is observed at 9 days after parturition
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• injection of oxytocin and/or prolactin does not rescue mortality/failure to thrive of litters tended by homozygous females
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• all pups nursed by homozygous females die before weaning, regardless of genotype
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• an accumulation of milk in the lumina of the alveoli is observed in the postpartum mutant mammary gland due to inefficient let-down
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• myoepithelial cells in mutant mammary tissues show dysfunction
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• at postpartum days 9 and 13, a marked increase in apoptotic cell death is observed in mutant mammary glands
• however, comparable numbers of apoptotic cells are noted in virgin and 5-day-postpartum mutant and wild-type mammary glands
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muscle
• mitochondria in some mutant muscle fibers are swollen and exhibit degeneration
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integument
• at 9 days after parturition, overall abundance of mammary gland tissue is similar, or even increased, in mutants vs wild-type
• at days 9 and 13 postpartum, a progressive loss of epithelial cell components and an increase in adipose tissue is observed
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• premature onset of involution-like process precludes sustained lactation beyond the first week after birth
|
• the mutant alveolar epithelium appears flattened in the initial postpartum
period, unlike in wild-type controls
• a progressive loss of epithelial cell components is noted at postpartum days 9 and 13 in mutant mammary glands
|
• the lumina of mutant mammary alveoli are full of milk and become dilated in the initial postpartum period (postpartum day 5)
|
• loss of the normal reddish-pink color of mammary gland tissue; a light yellow-tan color is observed at 9 days after parturition
|
• injection of oxytocin and/or prolactin does not rescue mortality/failure to thrive of litters tended by homozygous females
|
• all pups nursed by homozygous females die before weaning, regardless of genotype
|
• an accumulation of milk in the lumina of the alveoli is observed in the postpartum mutant mammary gland due to inefficient let-down
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• myoepithelial cells in mutant mammary tissues show dysfunction
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• at postpartum days 9 and 13, a marked increase in apoptotic cell death is observed in mutant mammary glands
• however, comparable numbers of apoptotic cells are noted in virgin and 5-day-postpartum mutant and wild-type mammary glands
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behavior/neurological
• an accumulation of milk in the lumina of the alveoli is observed in the postpartum mutant mammary gland due to inefficient let-down
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