mortality/aging
• Background Sensitivity: on a mixed genetic background, most homozygous mice die shortly after birth with a few (4.5%) survivors present at 4 weeks of age; on a 129 isogenic background, all homozygous mice die at birth
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endocrine/exocrine glands
• overall, adrenals appear disorganized
• normal formation of the zona glomerulosa
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• the expression of steroid biosynthetic enzymes is elevated 2-3 fold or more
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• hypertrophy, with increased production of corticosterone
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• hypertrophy, with increased production of corticosterone
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• prominent hypertrophy and possible hyperplasia of adrenal cortical cells, apparent by day 15 p.c.
• cells are enlarged 2-3 fold
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• at E18.5, a small number of tyrosine hydroxylase (TH)-expressing chromaffin cells are scattered among the enlarged cells of the cortex instead of in the medulla
• these cells do not express phenylethanolamine N-methyltransferase (PNMT) suggesting that these are noradrenergic chromaffin cells
• at E13.5 and E15.5, a greatly reduced number of chromaffin cells are present in adrenal glands in mutant embryos
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• among the scattered chromaffin cells present in the cortex, these do not express phenylethanolamine N-methyltransferase (PNMT) suggesting that these are noradrenergic chromaffin cells and that adrenergic cells are missing
• only noradrenaline-specific chromaffin granules are present in chromaffin cells
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• no central medulla of chromaffin cells is present in mice at E18.5
• in surviving adults, the medullary region is replaced by a mass of white adipose and loose, highly vascularized connective tissue
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• adrenal glands are approximately twice the size of controls
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homeostasis/metabolism
• total plasma level is increased 2-3 fold
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• total plasma levels are increased more than 20 fold
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• mutant adrenal glands contain no adrenaline
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• mutant adrenals contain a reduced amount of noradrenaline
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respiratory system
atelectasis
(
J:27441
)
• severe at birth, with little or no inflation of the lungs in dying animals
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• despite defects in branching morphogenesis of the bronchioles and alveoli, expression of surfactant protein genes in the developing respiratory epithelium and in the developing lung is similar to controls
• the number of type II alveolar cells is similar to controls
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• a reduction in the level of expression of amiloride-sensitive Na+ channel mRNA is seen; this may account for a reduction in sodium transport and water removal from the lungs before birth
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• impaired development of terminal bronchioles
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• impaired development of alveoli
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• at birth, homozygous mice exhibit respiratory distress
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liver/biliary system
• at birth, a reduction in the activation of gluconeogenic enzymes is seen, including G6pc (glucose-6-phosphatase), Tat (tyrosine aminotransferase) and Sds (serine dehydratase)
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nervous system
• at E18.5, a small number of tyrosine hydroxylase (TH)-expressing chromaffin cells are scattered among the enlarged cells of the cortex instead of in the medulla
• these cells do not express phenylethanolamine N-methyltransferase (PNMT) suggesting that these are noradrenergic chromaffin cells
• at E13.5 and E15.5, a greatly reduced number of chromaffin cells are present in adrenal glands in mutant embryos
|
• among the scattered chromaffin cells present in the cortex, these do not express phenylethanolamine N-methyltransferase (PNMT) suggesting that these are noradrenergic chromaffin cells and that adrenergic cells are missing
• only noradrenaline-specific chromaffin granules are present in chromaffin cells
|