Analysis Tools
hematopoietic system
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• homozygotes display normal kinetics of erythrocyte recovery after acute hemolysis induced by phenylhydrazine, as determined by measuring peripheral red cells, reticulocytes, and CFU-Es in bone marrow (BM) and spleen
• in addition, homozygotes show normal kinetics of recovery of BM progenitors after 5-fluorouracil-induced myelosuppression
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• homozygotes exhibit impaired hematopoiesis in the bone marrow, and increased hematopoiesis in the spleen
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• in clonal culture assays, homozygotes show a significant reduction in the number of CFU-GEMMs, CFU-MEs, and BFU-Es in the bone marrow (BM) relative to wild-type mice
• in contrast to the BM, the number of CFU-GEMMs, CFU-MEs, and BFU-Es in mutant spleen is elevated relative to that observed in wild-type mice
• whereas no significant differences are observed in the number of granulocyte-macrophage colony-forming cells (GM-CFCs), including granulocyte CFUs (CFU-Gs), macrophage CFUs (CFU-Ms), and granulocyte-macrophage CFUs (CFU-GMs) in the mutant BM, the numbers of all types of GM-CFCs in mutant spleen are elevated relative to wild-type mice, indicating an opposite effect on hematopoiesis in BM and spleen
• in BM transplantation experiments, neonatal homozygotes engrafted with wild-type BM cells fail to produce erythrocytic and megakaryocytic progenitors to the levels observed in wild-type mice, indicating an effect on the hematopoietic microenvironment
• conversely, wild-type mice reconstituted with homozygous mutant BM cells exhibit a reduction in erythrocytic and megakaryocytic progenitors in the BM, whereas the GM-CFC number remains unchanged
• interestingly, hematopoietic progenitors in spleen are increased in homozygotes engrafted with either wild-type or homozygoys mutant BM cells, whereas they are not increased in wild-type mice that receive either wild-type or mutant BM cells
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• homozygotes show a significant reduction in the number of mature megakaryocytes in the BM relative to wild-type mice, as measured in H&E stained femoral sections
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• in clonal culture assays, homozygotes show a significant reduction in the number of CFU-Es in the BM relative to wild-type mice
• in contrast to the BM, the number of CFU-Es in mutant spleen is significantly increased relative to that observed in wild-type mice
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• homozygotes show a significant reduction in the number of megakaryocyte progenitors, as determined in liquid cultures of BM cells
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• homozygotes show a significant reduction in the mean number of peripheral erythrocytes relative to wild-type mice (894 64 x 104/mL vs 1028 52 x 104/mL, respectively)
• in contrast, the mean number of peripheral white blood cells remains relatively unaffected
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• homozygotes display a reduced hematocrit relative to wild-type mice
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• homozygotes show a significant reduction in the mean number of peripheral platelets relative to wild-type mice (82 10 x 104/mL vs 106 15 x 104/mL, respectively)
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adipose tissue
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• mice fed a high-fat diet show increased weights of epididymal and subcutaneous adipose tissues compared to wild-type
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• mice fed a high-fat diet show increased weights of epididymal and subcutaneous adipose tissues compared to wild-type
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• mice fed a high-fat diet exhibit exacerbation of adipose tissue inflammation, with an increase in total number of F4/80-positive macrophages per weight of adipose tissue, with higher percentages of CD11c-positive M1-type and CD206-positive M2-type macrophages, lower percentage of CD11c/Cd2k06-double-negative cells among the total number of F4/80-positive macrophages and an increase in inflammatory markers
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growth/size/body
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• mice fed a high-fat diet develop obesity; mutants gain more weight than wild-type at 4 weeks on the high-fat diet and remain heavier
• however, in a pair-feeding study in which mutant mice receive the average amount of food consumed by wild-type mice, mutants show similar body weight to wild-type mice
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• mice fed a high-fat diet exhibit increased liver weight
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homeostasis/metabolism
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• mice fed a high-fat diet develop obesity; mutants gain more weight than wild-type at 4 weeks on the high-fat diet and remain heavier
• however, in a pair-feeding study in which mutant mice receive the average amount of food consumed by wild-type mice, mutants show similar body weight to wild-type mice
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• mice fed a high-fat diet begin to show an increase in blood glucose concentrations after 6 weeks on the diet
• mice fed a high-fat diet show increased blood glucose concentration under both fed and fasted states after 8 weeks of the diet
• in a pair-feeding study in which mutant mice receive the average amount of food consumed by wild-type mice, none of the metabolic phenotypes seen in mutants are affected by this decrease in food intake
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• mice fed a high-fat diet begin to show an increase in serum insulin concentration after 1 week on the diet and this continues to increase for 8 weeks
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• mice fed a high-fat diet show increased leptin serum concentration compared to wild-type
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• mice fed a high-fat diet exhibit increased serum total cholesterol concentrations in both fed and fasted states
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• mice fed a high-fat diet show a tendency for increased serum free fatty acids concentration in both fed and fasted states
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• mice fed a high-fat diet exhibit increased serum triglyceride concentrations in both fed and fasted states
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• mice fed a high-fat diet exhibit increased serum concentrations of IL-10
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• mice fed a high-fat diet exhibit increased serum concentrations of TNF-alpha
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• mice fed a high-fat diet show reduced glucose tolerance
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• mice fed a high-fat diet exhibit fewer glycogen granules in hepatocytes than wild-type mice
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• mice fed a high-fat diet develop insulin resistance
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• mice fed a high-fat diet show increased total cholesterol levels in the liver
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• mice fed a high-fat diet show increased triglyceride levels in the liver
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integument
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• mice fed a high-fat diet show increased weights of epididymal and subcutaneous adipose tissues compared to wild-type
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liver/biliary system
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• mice fed a high-fat diet exhibit increased liver weight
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• mice fed a high-fat diet exhibit fewer glycogen granules in hepatocytes than wild-type mice
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• mice fed a high-fat diet show increased total cholesterol levels in the liver
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• mice fed a high-fat diet show increased triglyceride levels in the liver
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• mice fed a high-fat diet exhibit severe hepatic steatosis
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endocrine/exocrine glands
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• mice fed a high-fat diet exhibit hyperplasia of beta-cells in pancreas
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immune system
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• mice fed a high-fat diet exhibit increased serum concentrations of IL-10
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• mice fed a high-fat diet exhibit increased serum concentrations of TNF-alpha
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• mice fed a high-fat diet exhibit increased serum concentrations of TNF-alpha, IL-10, and serum amyloid A, indicating elevation of systemic inflammation
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• mice fed a high-fat diet exhibit exacerbation of adipose tissue inflammation, with an increase in total number of F4/80-positive macrophages per weight of adipose tissue, with higher percentages of CD11c-positive M1-type and CD206-positive M2-type macrophages, lower percentage of CD11c/Cd2k06-double-negative cells among the total number of F4/80-positive macrophages and an increase in inflammatory markers
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behavior/neurological
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• mice fed a high-fat diet show increased amount of food intake compared to wild-type mice
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