Analysis Tools
growth/size/body
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• increase in left ventricle wall thickness and mass is seen by 6 months of age but not at 2 months of age
• induced weight loss via leptin infusion, but not via caloric restriction, partially resolves the hypertrophy
|
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• treatment with triiodothyronine significantly reduces body weight relative to the reduction seen in controls
(J:22025)
• body weight reduced by treatment with Leptin
(J:29075)
|
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• develop progressive obesity
(J:103063)
• 12-week old males are obese
(J:104171)
|
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• mice reach 60-70 g by 10 months of age
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homeostasis/metabolism
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• leptin-treated islet cells exhibit decreased insulin secretion compared to similarly treated wild-type islets
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• insulin content in the pancreata is increased compared to in wild-type mice
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• 4 weeks' treatment with Adipor2-ASO (antisense oligonucleotide) significantly reduces plasma glucose levels in fed mice
(J:129554)
• after feeding, serum glucose levels are more than 30% lower than in wild-type mice
(J:145998)
• when treated with AdipoR2-ASO, mice exhibit a decrease in plasma glucose level
(J:189019)
|
hypoglycemia
(
J:5400
)
|
• older mice are usually hypoglycemic
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• transient hyperglycemia
(J:5400)
• blood sugar peaks at 2-3 months
(J:5400)
• returns to normal by 4-5 months of age
(J:5400)
• Background Sensitivity: homozygotes exhibit a mild, transient hyperglycemia between 10-14 weeks of age as compared to the severe, progressive hyperglycemia observed on the BTBR background
(J:65486)
• mice infrequently transition to severe hyperglycemia
(J:65486)
• serum glucose is 320 mg/dl compared to 134 mg/dl in wild-type controls
(J:122746)
|
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• insulin levels increase rapidly to over 50X normal controls
(J:5400)
• seen in 12-week old males
(J:104171)
• serum insulin is 41.5 ng/ml compared to 0.8 ng/ml in wild-type
(J:122746)
|
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• fasting plasma total cholesterol concentration is increased 2-3 fold over controls
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• triglyceride levels are elevated 1.5- to 2-fold
(J:18161)
• seen in 12-week old males
(J:104171)
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• body temperature is maintained a basal level when the ambient temperature is gradually reduced to 4C
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• oxygen consumption about 2/3 that observed in controls
(J:22025)
• increased by treatment with triiodothyronine
(J:22025)
• insulin stimulated oxygen consumption by the soleus muscle is little affected by triiodothyronine
(J:22377)
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• in the epididymal and brown fat pads
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• in the liver
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• glucose intolerance which improved when treated with rosiglitazone
(J:107486)
• following an acute intraperitoneal glucose injection, the post-challenge glucose level remained elevated up to 120 min compared to controls, indicating glucose intolerance
(J:107486)
|
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• total body protein lower than in controls
• total body protein increased by treatment with triiodothyronine
|
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• males show elevated levels of serotonin and 5'hydroxyindolineacetic acid in urine
|
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• less epinephrine in the urine of ad libitum fed mice
• urine levels of norepinephrine only slightly elevated
• males show elevated levels of dopamine in urine
|
cardiovascular system
|
• exhibit myocyte hypertrophy, with increased myocyte diameter and distorted nuclear architecture
(J:103063)
• exhibit extensive focal damage in myocardial tissue, showing an abundance of lipid droplets in myocytes and damaged mitochondria that are swelled, have disorganized cristae and show loss of integrity
(J:104171)
• cardiomyocytes exhibit a significantly enlarged cross-sectional area
(J:111488)
|
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• cardiomyocytes display larger resting cell length and cross-sectional area
|
|
• increase in left ventricle wall thickness and mass is seen by 6 months of age but not at 2 months of age
• induced weight loss via leptin infusion, but not via caloric restriction, partially resolves the hypertrophy
|
|
• exhibit cardiac contractile dysfunction that is due to leptin deficiency and not obesity as high fat diet-induced obese controls show normal cardiomyocyte morphology and contractile function
(J:104171)
• decreased peak shortening
(J:111488)
• cardiomyocytes exhibit a reduced contractile capacity
(J:111488)
• prolonged relengthening
(J:111488)
• elevated resting peak calcium ion concentration
(J:111488)
• slowed intracellular calcium ion decay
(J:111488)
|
|
• cardiomyocytes exhibit decreased peak shortening and maximal velocity of shortening/relengthening, prolonged time-to-90% relengthening, reduced intracellular calcium release upon electrical stimulus associated with a slowed intracellular calcium decay rate, and significantly higher oxygen levels
|
muscle
|
• exhibit cardiac contractile dysfunction that is due to leptin deficiency and not obesity as high fat diet-induced obese controls show normal cardiomyocyte morphology and contractile function
(J:104171)
• cardiomyocytes exhibit a reduced contractile capacity
(J:111488)
• decreased peak shortening
(J:111488)
• prolonged relengthening
(J:111488)
• elevated resting peak calcium ion concentration
(J:111488)
• slowed intracellular calcium ion decay
(J:111488)
|
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• muscle protein content is reduced
|
|
• exhibit myocyte hypertrophy, with increased myocyte diameter and distorted nuclear architecture
(J:103063)
• exhibit extensive focal damage in myocardial tissue, showing an abundance of lipid droplets in myocytes and damaged mitochondria that are swelled, have disorganized cristae and show loss of integrity
(J:104171)
• cardiomyocytes exhibit a significantly enlarged cross-sectional area
(J:111488)
|
|
• cardiomyocytes display larger resting cell length and cross-sectional area
|
|
• increase in left ventricle wall thickness and mass is seen by 6 months of age but not at 2 months of age
• induced weight loss via leptin infusion, but not via caloric restriction, partially resolves the hypertrophy
|
|
• cross-sectional area of muscle fibers is generally smaller
|
|
• lower proportion of faster myosin heavy chain isoforms
|
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• mean muscle mass consistently less than controls but magnitude of difference is muscle specific
|
adipose tissue
|
• treatment with triiodothyronine significantly reduces adipocyte numbers relative to the degree of reduction seen in controls
• treatment with triiodothyronine reduces adipocyte numbers
|
|
• treatment with triiodothyronine significantly reduces epididymal fat pad weight relative to the degree of reduction seen in controls
• adipocyte size remains larger after treatment with triiodothyronine relative to controls
|
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• greater weight than for controls
• affected less by treatment with triiodothyronine than controls
• brown adipocyte numbers are normal
|
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• mice have fat mass of ~42 g compared to ~3 g in wild-type at 16 weeks
|
behavior/neurological
|
• food intake is reduced by Leptin treatment
|
|
• increased food intake when ambient temperature drops from 28 to 21C
|
polyphagia
(
J:122746
)
|
• mice eat 70% more than wild-type controls
|
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• less wheel running activity
(J:115771)
• more wheel running activity in light phase and less in dark phase
(J:115771)
• significantly reduced activity relative to wild-type controls
(J:122746)
|
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• increased total sleep time in a 24 hour period
• additional sleep primarily in the dark phase
• increased non-REM sleep time
• recovery from sleep deprivation involves increased duration of non-REM bouts rather than increased number of bouts as seen in controls
|
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• reduced REM in light phase
• increased REM in dark phase
|
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• sleep more fragmented
• more arousals
• shorter wake periods
|
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• resistant to tactile allodynia caused by partial sciatic nerve ligation
• epineural application of leptin treated peritoneal macrophage induces tactile allodynia
|
hyperalgesia
(
J:152019
)
|
• display thermal hyperalgesia after partial sciatic nerve ligation
|
reproductive system
 |
• females do not produce litters
|
respiratory system
|
• ozone induces significantly elevated levels of TNFR1
• ozone induces a nonsignificant elevation of TNFR2 levels
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endocrine/exocrine glands
|
• Background Sensitivity: less beta cell degranulation than seen on the "BKS" background
|
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• leptin-treated islet cells exhibit decreased insulin secretion compared to similarly treated wild-type islets
|
|
• insulin content in the pancreata is increased compared to in wild-type mice
|
renal/urinary system
|
• males show elevated levels of serotonin and 5'hydroxyindolineacetic acid in urine
|
|
• less epinephrine in the urine of ad libitum fed mice
• urine levels of norepinephrine only slightly elevated
• males show elevated levels of dopamine in urine
|
immune system
|
• reduced numbers can be restored by treatment with leptin
|
|
• ozone induces significantly elevated levels of TNFR1
• ozone induces a nonsignificant elevation of TNFR2 levels
|
neoplasm
|
• increased metastasis to the lung of both melanoma cell lines and lung cancer cell lines initially injected in the tail vein
• leptin reduces the level of metastasis
|
hematopoietic system
|
• reduced numbers can be restored by treatment with leptin
|
nervous system
liver/biliary system
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• treatment with triiodothyronine significantly reduces relative and absolute liver weight
|
skeleton
|
• bone marrow is almost completely replaced with mature adipocytes
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| obesity | DOID:9970 |
OMIM:601665 |
J:103063 , J:104171 | |
