mortality/aging
• litters from F3 generation mutant dams are smaller than those from cre-negative dams or mutants from the F1or F2 generations; litter size of female mutants of the F1 or F2 generations conform to the expected size
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growth/size/body
• 10 month-old F3 females show a significant increase in lean body mass; 3.5 month-old males and females and 10 month-old males do not exhibit any increase
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• growth rates are identical to controls up to 3 months of age but mean body weights for F3 generation males and females diverge from controls at 4 and 6.5 months, respectively
• at 9 months, F3 females are 46% heavier than controls but after 9 months, females lose weight with the average weight no longer being different from controls; males are significantly heavier than controls by 4 months of age with the difference continuing throughout life (at least 12-13 months)
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homeostasis/metabolism
N |
• serum leptin and insulin levels are not different from controls in 3-4 month-old F3 males or females (all young adult groups even if group contained obese animals); no changes are observed in serum Igf1 levels
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• leptin levels rise with obesity in older male and female mutants
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• levels are reduced by 72% in F3 generation adult males and by 50% in F3 female adults
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endocrine/exocrine glands
N |
• despite reduction in GH-positive somatotroph numbers, there is no change in overall number of pituitary cells, or changes in pituitary size or morphology
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• in F2 and F3 generation male and female mice, there is a significant decrease in growth hormone-positive cells
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adipose tissue
• some F3 generation animals were analyzed by DEXA (dual-energy x-ray absorptiometry) to look for changes in fat and lean mass
• 3.5 month-old F3 males show signficantl increases in grams of body fat; females show significant increases in fat mass at 3.5 and (in a small subset) at 10 months
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nervous system
• in F2 and F3 generation male and female mice, there is a significant decrease in growth hormone-positive cells
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reproductive system
N |
• timing of puberty is normal in mutants
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