Mouse Genome Informatics
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    Lepob/Lepob
B6.Cg-Lepob/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Lepob/Lepob

growth/size
• mice have fat mass of ~42 g compared to ~3 g in wild-type at 16 weeks
• 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)
• develop progressive obesity (J:103063)
• 12-week old males are obese (J:104171)
• mice reach 60-70 g by 10 months of age

homeostasis/metabolism
• 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
• after feeding, serum glucose levels are more than 30% lower than in wild-type mice
• older mice are usually hypoglycemic
• 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)
• males exhibit elevated blood glucose levels (254.4 +/-33.7 mg/dl) as compared to wild-type between 20-22 weeks of age (J:185261)
• Background Sensitivity: blood glucose levels are lower than obese mice on the BTBR background (J:185261)
• 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)
• at 2 weeks, insulin levels are increased 2.5-fold compared to in wild-type mice (J:145998)
• however, mice treated with isoproterenol exhibit lowered serum levels of insulin (J:145998)
• fasting plasma total cholesterol concentration is increased 2-3 fold over controls
• triglyceride levels are elevated 1.5- to 2-fold (J:18161)
• seen in 12-week old males (J:104171)
• body temperature is maintained a basal level when the ambient temperature is gradually reduced to 4C
• 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)
• in the epididymal and brown fat pads
• 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)
• total body protein lower than in controls
• total body protein increased by treatment with triiodothyronine
• 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

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)
• 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)
• 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)
• 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)
• 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
• cross-sectional area of muscle fibers is generally smaller
• lower proportion of faster myosin heavy chain isoforms
• 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
• mice have fat mass of ~42 g compared to ~3 g in wild-type at 16 weeks
• 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
• greater weight than for controls
• affected less by treatment with triiodothyronine than controls
• brown adipocyte numbers are normal

behavior/neurological
• food intake is reduced by Leptin treatment
• increased food intake when ambient temperature drops from 28 to 21C
• mice eat 70% more than wild-type controls
• 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)
• resistant to tactile allodynia caused by partial sciatic nerve ligation
• epineural application of leptin treated peritoneal macrophage induces tactile allodynia
• display thermal hyperalgesia after partial sciatic nerve ligation
• 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
• reduced REM in light phase
• increased REM in dark phase
• sleep more fragmented
• more arousals
• shorter wake periods

reproductive system
• females do not produce litters (J:122746)

respiratory system
• ozone induces significantly elevated levels of TNFR1
• ozone induces a nonsignificant elevation of TNFR2 levels

endocrine/exocrine glands
• Background Sensitivity: less beta cell degranulation than seen on the "BKS" background
• 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

tumorigenesis
• 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
• treatment with triiodothyronine significantly reduces relative and absolute liver weight

integument
• resistant to tactile allodynia caused by partial sciatic nerve ligation
• epineural application of leptin treated peritoneal macrophage induces tactile allodynia
• display thermal hyperalgesia after partial sciatic nerve ligation

skeleton
• bone marrow is almost completely replaced with mature adipocytes

Mouse Models of Human Disease
OMIM IDRef(s)
Obesity 601665 J:103063 , J:104171