Analysis Tools
mortality/aging
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• many pups die perinatally
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• fewer than the expected Mendelian ratio of pups is seen at weaning (only 17 out of 277 total pups)
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growth/size/body
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• mice fed a high-fat diet are slightly leaner than wild-type mice, although both show hepatic steatosis
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• pups are smaller at 2 days of age
• surviving mice have reduced body mass at 1 month of age, however by 4 months of age, mice weight the same as wild-type mice
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liver/biliary system
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• 30% increase in apoptosis in livers at 1 month of age
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• reduction in the number of binuclear hepatocytes and tetraploidy suggest impaired hepatic differentiation and maturation
• livers show continued presence of hematopoietic cells at 1 month of age unlike in wild-type mice which show only residual CD45-positive hematopoietic cells, however, numbers of circulating blood cells are normal indicating a defect in hepatocyte maturation rather than increase in extramedullary hematopoiesis
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• livers of surviving mice exhibit a roughened surface and multiple small nodules
• architecture of the liver is disturbed with large irregular hepatocytes, compressed sinusoidal spaces and bile canaliculi and clusters of small hematopoietic cells
• decrease in lipid droplets in the liver of 1 month old mice
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• compressed sinusoidal spaces
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• 60% decrease in stored glycogen in the liver
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• decrease in cholesterol in the liver at 1 month of age but not at 4 months of age
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• mice fed a high-fat diet do not show an increase in hepatic triglyceride levels as is seen in wild-type mice
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• compressed bile canaliculi
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• hepatocytes are larger with irregularly sized nuclei and dense mitotic figures
• reduction in the number of binuclear hepatocytes and tetraploidy suggesting impaired hepatic differentiation and maturation
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small liver
(
J:205756
)
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• surviving mice have smaller livers at 1 month of age
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pale liver
(
J:205756
)
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• surviving mice have pale livers at 1 month of age
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homeostasis/metabolism
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• decrease in fatty acid oxidation in the liver
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• mice fed a high-fat diet are slightly leaner than wild-type mice, although both show hepatic steatosis
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hypoglycemia
(
J:205756
)
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• mice exhibit fasting-induced hypoglycemia at 1 month of age however, fasting insulin levels are normal
• by 4 months of age, fasting blood glucose levels are normal
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• serum cholesterol is lower at 1 month of age on a normal diet and at 4 months of age on the high-fat diet
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• at 1 month of age
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• serum triglyceride levels are lower on a normal diet and are unchanged on a high-fat diet
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• total serum protein is decreased due to a 30% decrease in serum albumin
• however, blood urea nitrogen, calcium, and creatinine are normal
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• glucose tolerance tests at 4 months of age in mice fed a low-fat diet for 12 weeks show decreased glucose at 15 min but normal values at subsequent times
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• 60% decrease in stored glycogen in the liver
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• insulin tolerance tests at 4 months of age in mice fed a low-fat diet for 12 weeks show increased insulin sensitivity and an inability to correct insulin-induced hypoglycemia
• mice fed a high-fat diet for 12 weeks show increased insulin sensitivity compared to wild-type mice, with a greater drop in blood glucose during the insulin tolerance test
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• decrease in cholesterol in the liver at 1 month of age but not at 4 months of age
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• mice fed a high-fat diet do not show an increase in hepatic triglyceride levels as is seen in wild-type mice
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adipose tissue
cardiovascular system
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• compressed sinusoidal spaces
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cellular
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• the rough endoplasmic reticulum (ER) is dilated in the liver, indicating ER stress
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• 30% increase in apoptosis in livers at 1 month of age
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• decrease in fatty acid oxidation in the liver
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endocrine/exocrine glands
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• impaired thymic development
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hematopoietic system
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• impaired thymic development
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immune system
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• impaired thymic development
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renal/urinary system
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• impaired kidney development
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