growth/size/body
• at 52 weeks of age, females exhibit a significant reduction in total fat mass and are on average 9.7% less fat than wild-type controls
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• both sexes are significantly lighter than wild-type and heterozygous littermates
• from 5 to 30 weeks of age, males are 5.8% lighter while females are 6.4% lighter than wild-type controls
• in females, the weight difference becomes significant at 2 weeks of age and increases to 15.9% from 30 to 50 weeks of age
• in males, the onset of the weight phenotype is delayed or the impact is less pronounced to reach significance at early time points
• at 52 weeks of age, the weight difference is primarily due to reduced fat deposition as both skeletal size (bone lengths) and bone mineral densities are normal
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adipose tissue
• at 52 weeks of age, females show a significant reduction in subcutaneous fat relative to wild-type controls
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• at 52 weeks of age, females show a significant reduction in abdominal fat relative to wild-type controls
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• at 52 weeks of age, females exhibit a significant reduction in total fat mass and are on average 9.7% less fat than wild-type controls
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• at 52 weeks of age, females exhibit a significant reduction in percent body fat/body weight relative to wild-type controls (21.6% vs 31.3%)
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behavior/neurological
• at 12-14 weeks of age, females, but not males, show a modest (13.8%) decrease in food intake relative to wild-type controls
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homeostasis/metabolism
• following prolonged exposure to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) to induce malignant bladder carcinomas, fewer females develop invasive tumors relative to wild-type controls (44% vs 83%) primarily due to a decreased occurrence of early lesions invading into connective tissue (13% vs 39%) as opposed to later, more malignant lesions invading into the muscle layer (31% vs 44%)
• however, no significant differences are noted in the incidence of early hyperplastic lesions or in total tumor burden
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• males, but not females, exhibit a modest but significant delay in skin wound healing kinetics relative to wild-type controls
• however, the histological appearance of incisional back skin wounds is normal at day 3, 7, 10 post-wounding and after healing at day 15
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neoplasm
N |
• following subcutaneous engraftment of Lewis Lung carcinoma cells, females show normal tumor take (100%) and tumor growth kinetics until day 12 post-injection relative to wild-type controls
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• following prolonged exposure to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) to induce malignant bladder carcinomas, fewer females develop invasive tumors relative to wild-type controls (44% vs 83%) primarily due to a decreased occurrence of early lesions invading into connective tissue (13% vs 39%) as opposed to later, more malignant lesions invading into the muscle layer (31% vs 44%)
• however, no significant differences are noted in the incidence of early hyperplastic lesions or in total tumor burden
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integument
N |
• surprisingly, at 52 weeks of age, females lack obvious histological epidermal phenotypes and show normal squamous epithelia morphology at various locations (including back skin, hair follicles, footpads, tongue, esophagus, non-glandular stomach, vagina and cornea) relative to wild-type controls
• TEM analysis of back skin from 10-week-old males showed no obvious membrane phenotypes at the subcellular level
• newborn pups show normal kinetics of trans-epidermal water loss (TEWL) relative to wild-type controls
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• at 52 weeks of age, females show a significant reduction in subcutaneous fat relative to wild-type controls
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