mortality/aging
• newborn homozygous mutant mice appeared normal and were indistinguishable from their littermates; however, 48 hours later, they exhibited growth retardation and dehydration and died within three days of birth
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endocrine/exocrine glands
N |
• homozygous mutant newborn mice had a pancreas with a normal macroscopic appearance
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• mice lacking both genes failed to develop any mature endocrine cells, suggesting that both genes are essential for endocrine cell differentiation during pancreatic development
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• at E10.5, insulin-producing beta and glucagon-producing alpha cells were detected in the pancreas of both wild-type and homozygous mutant embryos
• notably, few - if any - insulin-producing beta cells were found in the pancreas of mutant newborn mice, whereas glucagon-producing alpha cells were numerous and abnormally clustered; in contrast, in wild-type newborn pancreas, most of the endocrine cells were beta cells, with alpha cells representing only a small fraction
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• expression analysis of somatostatin, an endocrine marker specific for delta cells, revealed that somatostatin-producing delta cells were also absent in the pancreas of homozygous mutant newborns
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• pancreas from 3 day-old wild-type mice displayed little or no expression of the pancreatic digestive enzyme alpha-amylase; surprisingly, pancreas from 3 day-old homozygous mutant mice showed a strong expression of alpha-amylase in all exocrine cells, suggesting that they might not be able to secret their enzymes into the digestive tract
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