Analysis Tools
mortality/aging
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• gamma irradiated homozygotes exhibit premature hair greying and hair loss, and an increased rate of tumor formation
• at 22 weeks after irradiation, all homozygotes exhibit hair greying while 30% also show large areas of hair loss on the back or around neck and mouth (not found in any wild-type)
• at 7 months after irradiation, all mutant males display teratomas (not found in any wild-type)
• at 16 months after irradiation, all mutants with malignant lymphomas display severe morbidity
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• 30% of homozygotes die before the age of 16 months, with the first death noted at 9 months
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• mutant females exhibit accelerated reproductive ageing, as indicated by a higher incidence of irregular oestrous cycles and a lower reproductive success at 9-12 months of age
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reproductive system
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• male mice months 18 months of age have enlarged preputial glands with severe duct ectasia, focal hyperplasia, and hyperkeratosis
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• mutant females exhibit accelerated reproductive ageing, as indicated by a higher incidence of irregular oestrous cycles and a lower reproductive success at 9-12 months of age
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• middle-aged female mutants are acyclic for ~45% of a 6-week observation period, whereas age-matched wild-type females never show acyclicity
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• middle-aged female mutants display significantly less regular 4-day estrous and more prolonged cycles (>6 days) for ~55% of a 6-week observation period
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• unlike wild-type, middle-aged mutant females exhibit a significantly higher number of embryonic scars (implantations) in the uterus after two pregnancies than the total number of live offspring detected at birth or at weanining, suggesting post-implantation embryo loss due to insufficient energy levels
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• primiparous (first parturition) mutant females fail to breed successfully whereas mutiparous (second parturition) mutant females yield significantly smaller litter sizes than wild-type females
• both primiparous and multiparous middle-aged (9-12 months of age) mutant females exhibit a lower reproductive success (either fewer litters or smaller litter sizes) than middle-aged wild-type females
• however, young adult mutant females (2-6 months of age) show the same success in fertility and fecundity as wild-type females
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• mutiparous (second parturition) mutant females yield significantly smaller litter sizes than wild-type females
• middle-aged (9-12 months of age) female mutants produce significantly smaller litter sizes than young adult (2-6 months of age) wild-type or mutant females
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behavior/neurological
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• homozygotes display normal wheel-running activity in constant darkness, suggesting that loss of circadian rhythmicity is not due to a decrease in total activity
(J:56167)
• homozygotes exhibit normal learning abilities in a fear conditioning paradigm (unpublished)
(J:77340)
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• in response to acute i.p. cocaine injections (10 mg/kg), both wild-type and mutant mice display a similar (~5-fold) increase in locomotor activity from saline control levels
• however, after repeated cocaine administration, homozygotes show a hypersensitized behavioral response to cocaine relative to wild-type mice
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• homozygotes exhibit a pronounced preference to the cocaine-paired side in the conditioned place preference (CPP) paradigm; however, this response is not statistically different from that of wild-type mice
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• unlike pregnant wild-type females which show a progressive increase in food intake that correlates positively with body mass, middle-aged mutant females do not significantly increase their food intake during pregnancy
• whereas middle-aged wild-type females increase their food intake by 67.6% up to the 16th day of lactation, age-matched mutant females increase their food consumption by 40%; moreover, this increase fails to occur continuously as in wild-type females
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• unlike non-reproductive wild-type females which prefer 20% protein content, middle-aged non-reproductive mutant females do not display any preference to a certain protein content
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• homozygotes show elevated locomotor activity in a several-hour period preceding the light-to-dark transition (pre-dusk activity)
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• homozygotes entrain to the LD cycle (12 h light/12 h dark) but display a significantly shorter circadian period in constant darkness
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• homozygotes exhibit loss of persistent circadian rhythmicity within 3 weeks in constant darkness (DD)
• most homozygotes do not lose their circadian rhythms immediately upon entry into DD
• upon loss of rhythmicity, a light pulse immediately restores their rhythms, indicating a partially functional clock
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• homozygotes exhibit less NREM sleep and REM sleep than wild-type in the last 3 hours before dark onset
• homozygotes have more NREM sleep than wild-type in the first 2 hours after light onset
• at the light-dark transition, mutants initiate their waking episode earlier than wild-type, suggesting that the sleep/wake pattern is not masked by light
• notably, sleep homeostasis reflected by the slow-wave activity (SWA) increase after 6 hours of sleep deprivation is preserved
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• unlike wild-type females, middle-aged mutant females spend an equal time in the nest during the three lactating stages (day 1, 11, and 21 of lactation)
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• all pups born to primiparous (first parturition) mutant females are cannibalised by their mothers
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neoplasm
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• 15% of homozygotes die of lymphoma before the age of 16 months
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• homozygotes exhibit a significantly higher frequency of tumor development than wild-type following gamma irradiation
• at 16 months after irradiation, 71% of irradiated mutants (versus only 5% of irradiated wild-type) develop malignant lymphomas in multiple organs
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skeleton
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• at 3, 12, and 48 weeks, but not 24 weeks
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• mice exhibit increased bone formation rate compared with wild-type mice
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cellular
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• mutant thymocytes exhibit a partial resistance to gamma radiation-induced apoptosis
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nervous system
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• homozygotes show no anatomical defects in the suprachiasmatic nucleus of the anterior hypothalamus
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digestive/alimentary system
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• at 6 months, both male and female homozygotes begin to develop salivary gland hyperplasia
• by 12 months, all unirradiated homozygotes show hyperplasia of major and minor salivary glands
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renal/urinary system
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• male mice months 18 months of age have enlarged preputial glands with severe duct ectasia, focal hyperplasia, and hyperkeratosis
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growth/size/body
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• loss of body mass after parturition is less pronounced in middle-aged mutant females than in middle-aged wild-type females
• unlike lactating wild-type females, middle-aged mutant females show no significant changes in body mass over a 21-day lactation period
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• middle-aged mutant females are significantly heavier than wild-type females both during the non-reproductive and pregnant stages
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homeostasis/metabolism
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• middle-aged mutant females exhibit a lower average daily metabolic rate than age-matched wild-type females both during the non-reproductive and reproductive (pregnancy and lactation) periods
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• gamma irradiated homozygotes exhibit premature hair greying and hair loss, and an increased rate of tumor formation
• at 22 weeks after irradiation, all homozygotes exhibit hair greying while 30% also show large areas of hair loss on the back or around neck and mouth (not found in any wild-type)
• at 7 months after irradiation, all mutant males display teratomas (not found in any wild-type)
• at 16 months after irradiation, all mutants with malignant lymphomas display severe morbidity
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integument
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• male mice months 18 months of age have enlarged preputial glands with severe duct ectasia, focal hyperplasia, and hyperkeratosis
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endocrine/exocrine glands
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• at 6 months, both male and female homozygotes begin to develop salivary gland hyperplasia
• by 12 months, all unirradiated homozygotes show hyperplasia of major and minor salivary glands
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• male mice months 18 months of age have enlarged preputial glands with severe duct ectasia, focal hyperplasia, and hyperkeratosis
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