mortality/aging
• 15% (18 of 119 mice) die over 42 days after TM treatment
• 46% of mice younger than 30 days at the beginning of TM treatment die within 42 days after TM treatment
• 12% of mice die if they are older than 30 days (up to 56 days) at the beginning of TM treatment
|
growth/size/body
• hearts are disproportionately large
|
• decreased growth
• attaining only 70% of normal weight
• no decrease in their consumption of food
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weight loss
(
J:155421
)
• during the first 3 weeks after TM treatment, rapid loss of weight
|
• all the phenotypes below are induced by tamoxifen (TM) treatment
• 5% smaller average body length (p<0.08)
|
• resistant to high-fat diet induced obesity
|
• kidneys are disproportionately large
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behavior/neurological
polyphagia
(
J:155421
)
• higher than normal food intake
• within a week after TM treatment increased food consumption (125%) which continues up to 8 months
|
• 53% (95 of 180) of surviving mice appear ''scruffy'', versus 3% (8 of 244) of wild type
|
• enhanced startle response
|
• most mice (96 of 180) are strikingly hyperkinetic in the open field test
|
• travel 3-fold greater distance in an open field
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• 3.1% mice (38 of 1,232) have tonic-clonic seizures during routine cage changes and handling of mice, versus 0.3% of wild type mice
|
adipose tissue
• strikingly lower content of the peritoneal white adipose tissue (WAT), on average only 16% of WAT in wild type mice
|
• contain little or no visceral fat
|
• decrease average diameter of intrascapular brown adipocytes
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• the average diameter of WAT adipocytes is 30% of that of the wild type mice
|
• exhibit ectopic induction of the uncoupling protein 1 (Ucp1) in white adipose tissue
|
homeostasis/metabolism
• resistant to high-fat diet induced obesity
|
• strongly hypersensitive to cold
|
• decreased fasting blood glucose level (88.6 mg/dl versus 125.3 mg/dl)
• lower glucose levels 6 hr after administration of glucose (80.9 mg/dl versus 109.7 mg/dl)
• no other significant differences in blood composition
|
• lower core body temperature on average 35.1C (36.7C in wild type)
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• the average water content and dry weight was 80.5% and 19.5%, respectively, versus 79.9% and 20.1% of wild type brains
|
• increased metabolic rate (resting metabolic rate, RMR)
• consume on average 46.12 ml of oxygen per kg per min, versus 29.3 ml of oxygen per kg per min
• decreased expression of mRNA encoding proopiomelanocortin (POMC) in hypothalami
• normal respiratory exchange ratio (RER)
|
nervous system
• 3.1% mice (38 of 1,232) have tonic-clonic seizures during routine cage changes and handling of mice, versus 0.3% of wild type mice
|
• the average water content and dry weight was 80.5% and 19.5%, respectively, versus 79.9% and 20.1% of wild type brains
|
• brains appear swollen and bigger
|
• the average brain weight, as a percentage of total body weight (TBW) are 3.09%, versus 1.96% of wild type mice
• no differences in cell proliferation (5-ethynyl-29-deoxyuridine (EdU) incorporation)
|
skeleton
• the skulls appear to be thinner and softer
|
• 66% (109 of 180) of surviving mice have a kyphotic posture, versus 2% (5 of 244) of wild type
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reproductive system
• lumens of seminiferous tubules contain few sperm cells, in a disorganized arrangement
|
• lumens of seminiferous tubules contain few sperm cells
|
• testis extracts contain the 85-kDa fragment of poly(ADP-ribose)-polymerase (PARP) but no full-length PARP, indicating extensive apoptosis
|
• males are infertile
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cardiovascular system
• hearts are disproportionately large
|
renal/urinary system
• kidneys are disproportionately large
|
cellular
• lumens of seminiferous tubules contain few sperm cells, in a disorganized arrangement
|
• lumens of seminiferous tubules contain few sperm cells
|
• increased retention of 14C in their brains, livers, spleens, kidneys and hearts
|
digestive/alimentary system
• increased intestinal import of 14C-protein
|
pigmentation
• 10% (8 of 80) of surviving mice develop patches of red hair among their normally black hair
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endocrine/exocrine glands
• testis extracts contain the 85-kDa fragment of poly(ADP-ribose)-polymerase (PARP) but no full-length PARP, indicating extensive apoptosis
|
craniofacial
• the skulls appear to be thinner and softer
|
integument
• 10% (8 of 80) of surviving mice develop patches of red hair among their normally black hair
|