All Phenotypes Ate1<tm1Avar> MGI Mouse

premature death ( J:155421 )

• 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

increased heart weight ( J:155421 )

• hearts are disproportionately large

slow postnatal weight gain ( J:155421 )

• decreased growth

• attaining only 70% of normal weight

• no decrease in their consumption of food

weight loss ( J:155421 )

• during the first 3 weeks after TM treatment, rapid loss of weight

decreased body length ( J:155421 )

• all the phenotypes below are induced by tamoxifen (TM) treatment

• 5% smaller average body length (p<0.08)

decreased susceptibility to diet-induced obesity ( J:155421 )

• resistant to high-fat diet induced obesity

increased kidney weight ( J:155421 )

• kidneys are disproportionately large

polyphagia ( J:155421 )

• higher than normal food intake

• within a week after TM treatment increased food consumption (125%) which continues up to 8 months

poor grooming ( J:155421 )

• 53% (95 of 180) of surviving mice appear ''scruffy'', versus 3% (8 of 244) of wild type

increased startle reflex ( J:155421 )

• enhanced startle response

hyperactivity ( J:155421 )

• most mice (96 of 180) are strikingly hyperkinetic in the open field test

increased locomotor activity ( J:155421 )

• travel 3-fold greater distance in an open field

seizures ( J:155421 )

• 10-fold higher propensity for seizures

tonic-clonic seizures ( J:155421 )

• 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

decreased white adipose tissue amount ( J:155421 )

• strikingly lower content of the peritoneal white adipose tissue (WAT), on average only 16% of WAT in wild type mice

decreased abdominal adipose tissue amount ( J:155421 )

• contain little or no visceral fat

decreased brown fat cell size ( J:155421 )

• decrease average diameter of intrascapular brown adipocytes

decreased white fat cell size ( J:155421 )

• the average diameter of WAT adipocytes is 30% of that of the wild type mice

abnormal white adipose tissue physiology ( J:155421 )

• exhibit ectopic induction of the uncoupling protein 1 (Ucp1) in white adipose tissue

decreased susceptibility to diet-induced obesity ( J:155421 )

• resistant to high-fat diet induced obesity

impaired adaptive thermogenesis ( J:155421 )

• strongly hypersensitive to cold

decreased circulating glucose level ( J:155421 )

• 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

decreased core body temperature ( J:155421 )

• lower core body temperature on average 35.1C (36.7C in wild type)

cerebral edema ( J:155421 )

• 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 basal metabolism ( J:155421 )

• 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)

seizures ( J:155421 )

• 10-fold higher propensity for seizures

tonic-clonic seizures ( J:155421 )

• 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

cerebral edema ( J:155421 )

• 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 brain size ( J:155421 )

• brains appear swollen and bigger

increased brain weight ( J:155421 )

• 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)

abnormal cranium morphology ( J:155421 )

• the skulls appear to be thinner and softer

kyphosis ( J:155421 )

• 66% (109 of 180) of surviving mice have a kyphotic posture, versus 2% (5 of 244) of wild type

abnormal spermatid morphology ( J:155421 )

• lumens of seminiferous tubules contain few sperm cells, in a disorganized arrangement

decreased male germ cell number ( J:155421 )

• lumens of seminiferous tubules contain few sperm cells

abnormal testis development ( J:155421 )

• testis extracts contain the 85-kDa fragment of poly(ADP-ribose)-polymerase (PARP) but no full-length PARP, indicating extensive apoptosis

male infertility ( J:155421 )

• males are infertile