Strain Name:

BKS.V-Lepob/J

Stock Number:

000696

Availability:

Repository-Cryopreserved

Description

Strain Information

Type Congenic; Mutant Strain;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
Background Strain C57BLKS/J
Donor Strain V
H2 Haplotyped
GenerationN5 F34

Appearance
black, fat
Related Genotype: a/a Lepob/Lepob

black, lean
Related Genotype: a/a Lepob/+ or a/a ?/+

Description
Mice homozygous for the obese spontaneous mutation (Lepob, commonly referred to as ob or ob/ob) are first recognizable at about 4 weeks old. Homozygous mutant mice increase in weight rapidly and may reach three times the normal weight of wildtype controls. In addition to obesity, mutant mice exhibit hyperphagia; a diabetes-like syndrome of hyperglycemia, glucose intolerance, and elevated plasma insulin; subfertility; and increased hormone production from both pituitary and adrenal. They are also hypometabolic and hypothermic. The obesity is characterized by both an increased number and size of adipocytes. Although hyperphagia contributes to the obesity, homozygotes gain excess weight and deposit excess fat even when restricted to a diet sufficient for normal weight maintenance in lean mice. Hyperinsulinemia does not develop until after the increase body weight and is probably the result of it. Homozygotes do have an abnormally low threshold for stimulation of pancreatic islet insulin secretion even in very young preobese animals. As is the case with the diabetes mutant (Lepdb), manifestation of the diabetic syndrome is strikingly dependent on genetic background. On the C57BLKS background Lepob/Lepobhomozygotes become severely diabetic with regression of islets and early death. Cloning of the Lep gene has made possible the production of recombinant leptin. Injection of this protein into Lepob/Lepob homozygotes sharply reduced body weight, decreased food intake, and increased energy expenditure.

Control Information

  Control
   Untyped from the colony
   000662 C57BLKS/J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Lepob allele
006906   B6.Cg-Lepob Ldlrtm1Her/J
000632   B6.V-Lepob/J
004824   BTBR.V(B6)-Lepob/WiscJ
View Strains carrying   Lepob     (3 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Lepob/Lepob

        BKS.V-Lepob/J
  • homeostasis/metabolism phenotype
  • abnormal circulating cholesterol level (MGI Ref ID J:18161)
    • increased circulating cholesterol level (MGI Ref ID J:18161)
      • fasting plasma total cholesterol concentration is increased 2-3 fold over controls
      • increased circulating HDL cholesterol level (MGI Ref ID J:18161)
      • increased circulating LDL cholesterol level (MGI Ref ID J:18161)
      • increased circulating VLDL cholesterol level (MGI Ref ID J:18161)
  • increased circulating triglyceride level (MGI Ref ID J:18161)
    • triglyceride levels are elevated 1.5- to 2-fold

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Lepob/Lep+

        involves: 129X1/SvJ * C57BL/6
  • liver/biliary system phenotype
  • increased liver weight (MGI Ref ID J:76479)
    • mice show significant increase in relative and absolute hepatic weight compared to wild-type; otherwise, no differences from wild-type are noted

Lepob/Lep+

        involves: C57BL/6J
  • skeleton phenotype
  • increased bone mass (MGI Ref ID J:60001)
    • increased bone mass even on a low fat diet to delay obesity

Lepob/Lepob

        involves: C57BL/6J
  • skeleton phenotype
  • abnormal skeleton development (MGI Ref ID J:60001)
    • rate of new bone formation increased at both 3 and 6 months
    • abnormal osteoclast differentiation (MGI Ref ID J:60001)
      • increased numbers of osteoclasts
  • increased bone mass (MGI Ref ID J:60001)
    • denser vertebrae and long bones at 6 months
    • increased bone mass even on a low fat diet to delay obesity
    • osteopetrosis (MGI Ref ID J:60001)
      • increased numbers of thick trabeculae at 3 and 6 months
      • 2 fold increase in trabecular bone volume
  • homeostasis/metabolism phenotype
  • increased circulating corticosterone level (MGI Ref ID J:60001)
    • severe
  • hematopoietic system phenotype
  • abnormal osteoclast differentiation (MGI Ref ID J:60001)
    • increased numbers of osteoclasts
  • immune system phenotype
  • abnormal osteoclast differentiation (MGI Ref ID J:60001)
    • increased numbers of osteoclasts

Lepob/Lepob

        B6.V-Lepob/J
  • growth/size phenotype
  • obese (MGI Ref ID J:104171)
    • 12-week old males are obese
    • develop progressive obesity
  • homeostasis/metabolism phenotype
  • abnormal circulating cholesterol level (MGI Ref ID J:18161)
    • increased circulating cholesterol level (MGI Ref ID J:18161)
      • fasting plasma total cholesterol concentration is increased 2-3 fold over controls
      • increased circulating HDL cholesterol level (MGI Ref ID J:18161)
      • increased circulating LDL cholesterol level (MGI Ref ID J:18161)
      • increased circulating VLDL cholesterol level (MGI Ref ID J:18161)
  • hyperglycemia (MGI Ref ID J:122746)
    • serum glucose is 320 mg/dl compared to 134 mg/dl in wild-type controls
  • impaired glucose tolerance (MGI Ref ID J:104171)
    • glucose intolerance which improved when treated with rosiglitazone
    • following an acute intraperitoneal glucose injection, the post-challenge glucose level remained elevated up to 120 min compared to controls, indicating glucose intolerance
  • increased circulating insulin level (MGI Ref ID J:104171)
    • seen in 12-week old males
    • serum insulin is 41.5 ng/ml compared to 0.8 ng/ml in wild-type
  • increased circulating triglyceride level (MGI Ref ID J:104171)
    • seen in 12-week old males
    • triglyceride levels are elevated 1.5- to 2-fold
  • insulin resistance (MGI Ref ID J:104171)
  • cardiovascular system phenotype
  • abnormal myocardial fiber morphology (MGI Ref ID J:104171)
    • 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
    • exhibit myocyte hypertrophy, with increased myocyte diameter and distorted nuclear architecture
    • enlarged myocardial fiber (MGI Ref ID J:104171)
      • cardiomyocytes display larger resting cell length and cross-sectional area
  • abnormal myocardial fiber physiology (MGI Ref ID J:104171)
    • 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
  • decreased cardiac muscle contractility (MGI Ref ID J:104171)
    • 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
  • left ventricle hypertrophy (MGI Ref ID J:103063)
    • 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
  • muscle phenotype
  • abnormal myocardial fiber morphology (MGI Ref ID J:104171)
    • 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
    • exhibit myocyte hypertrophy, with increased myocyte diameter and distorted nuclear architecture
    • enlarged myocardial fiber (MGI Ref ID J:104171)
      • cardiomyocytes display larger resting cell length and cross-sectional area
  • decreased cardiac muscle contractility (MGI Ref ID J:104171)
    • 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
  • adipose tissue phenotype
  • increased adipose tissue amount (MGI Ref ID J:122746)
    • mice have fat mass of ~42 g compared to ~3 g in wild-type at 16 weeks
  • behavior/neurological phenotype
  • abnormal food intake (MGI Ref ID J:122746)
    • polyphagia (MGI Ref ID J:122746)
      • mice eat 70% more than wild-type controls
  • hypoactivity (MGI Ref ID J:122746)
    • significantly reduced activity relative to wild-type controls
  • reproductive system phenotype
  • female infertility (MGI Ref ID J:122746)
    • females do not produce litters
  • respiratory system phenotype
  • lung inflammation (MGI Ref ID J:115772)
    • ozone induces significantly elevated levels of TNFR1
    • ozone induces a nonsignificant elevation of TNFR2 levels
  • immune system phenotype
  • decreased NK cell number (MGI Ref ID J:117826)
    • reduced numbers can be restored by treatment with leptin
  • lung inflammation (MGI Ref ID J:115772)
    • ozone induces significantly elevated levels of TNFR1
    • ozone induces a nonsignificant elevation of TNFR2 levels
  • tumorigenesis
  • increased metastatic potential (MGI Ref ID J:117826)
    • 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 phenotype
  • decreased NK cell number (MGI Ref ID J:117826)
    • reduced numbers can be restored by treatment with leptin

Lepob/Lepob

        D2.B6-Lepob
  • growth/size phenotype
  • obese (MGI Ref ID J:78850)
  • homeostasis/metabolism phenotype
  • hyperglycemia (MGI Ref ID J:78850)
    • at 3 months of age, males are hyperglycemic with blood glucose levels of ~574 mg/dl; females have levels of ~388 mg/dl
  • increased circulating insulin level (MGI Ref ID J:78850)
    • some mutant DBA/2J mice have high insulin levels compared to controls
  • endocrine/exocrine gland phenotype
  • abnormal pancreatic islet morphology (MGI Ref ID J:78850)
    • islets of mutants with low insulin levels are abnormal in appearance, being found in clusters of 1-4 cells, scattered within the ductal epithelium
    • decreased pancreatic beta cell number (MGI Ref ID J:78850)
      • mutants with low insulin secretion have a low number of insulin-secreting cells compared to controls or high-insulin secreting mutants
    • increased pancreatic beta cell number (MGI Ref ID J:78850)
      • there is a 5-fold increase in number of insulin-secreting cells per islet in obese mice with high insulin secretion
  • digestive/alimentary phenotype
  • abnormal pancreatic islet morphology (MGI Ref ID J:78850)
    • islets of mutants with low insulin levels are abnormal in appearance, being found in clusters of 1-4 cells, scattered within the ductal epithelium
    • decreased pancreatic beta cell number (MGI Ref ID J:78850)
      • mutants with low insulin secretion have a low number of insulin-secreting cells compared to controls or high-insulin secreting mutants
    • increased pancreatic beta cell number (MGI Ref ID J:78850)
      • there is a 5-fold increase in number of insulin-secreting cells per islet in obese mice with high insulin secretion

Lepob/Lepob

        FVB.B6-Lepob
  • homeostasis/metabolism phenotype
  • hyperglycemia (MGI Ref ID J:78850)
    • mice are hyperglycemic like congenic FVB Lepr mice
  • increased circulating insulin level (MGI Ref ID J:78850)
    • mice are hyperinsulinemic like congenic FVB Leprdb mice

Lepob/Lepob

        involves: 129X1/SvJ * C57BL/6
  • growth/size phenotype
  • decreased lean body mass (MGI Ref ID J:107169)
    • decreased (16.0 g, 33% of body weight) compared to wild-type (25.5 g 87% of body weight) or double mutants (19.8g)
  • increased body weight (MGI Ref ID J:107169)
    • higher than wild-type
  • homeostasis/metabolism phenotype
  • abnormal circulating hormone level (MGI Ref ID J:76479)
    • abnormal circulating pancreatic peptide level (MGI Ref ID J:76479)
      • plasma levels of pancreatic polypeptide (PP) are strongly reduced compared to wild-type
    • decreased circulating testosterone level (MGI Ref ID J:76479)
      • level is markedly decreased compared to wild-type or Lep heterozygotes
      • significantly lower (4.2 nmol/l) compared to wild-type (14.2 nmol/l)
    • increased circulating corticosterone level (MGI Ref ID J:76479)
      • mice display hypercorticosteronemia compared to wild-type
      • mice display hypercorticosteronemia compared to wild-type, Npy2rtm1.1Hhz homozygotes, or Npy2r, Lep double mutants
    • increased circulating insulin level (MGI Ref ID J:76479)
      • level is significantly increased over wild-type
      • hyperinsulinemic compared to wild-type
    • increased circulating leptin level (MGI Ref ID J:76479)
      • level is significantly increased over wild-type
  • hyperglycemia (MGI Ref ID J:107169)
  • increased circulating cholesterol level (MGI Ref ID J:107169)
    • 5.74 mmol/l vs 3.54 mmol/l in wild-type
  • increased circulating triglyceride level (MGI Ref ID J:107169)
    • 2.48 mmol/l vs 1.62 mmol/l in wild-type
  • endocrine/exocrine gland phenotype
  • abnormal branching of the mammary ductal tree (MGI Ref ID J:76479)
    • in virgin females, no ductal development occurs
  • abnormal ovarian folliculogenesis (MGI Ref ID J:76479)
    • ovaries have very few primary or secondary follicles
  • absent corpus luteum (MGI Ref ID J:76479)
    • no corpora lutea develops properly in ovary
  • decreased seminal gland weight (MGI Ref ID J:76479)
    • weight of gland is significantly lower than wild-type or heterozygotes
  • decreased testis weight (MGI Ref ID J:76479)
    • testis weight is significantly lower than in Lepob heterozygotes or Lep, Ppyr1 double null mice
    • testes weigh 0.19 g compared to 0.33 g in wild-type
  • increased pancreas weight (MGI Ref ID J:107169)
    • 0.41 g vs 0.29 in wild-type
  • adipose tissue phenotype
  • abnormal adipose tissue amount (MGI Ref ID J:107169)
    • combined white adipose tissue (WAT) mass is increased compared to wild-type
  • reproductive system phenotype
  • abnormal branching of the mammary ductal tree (MGI Ref ID J:76479)
    • in virgin females, no ductal development occurs
  • abnormal ovarian folliculogenesis (MGI Ref ID J:76479)
    • ovaries have very few primary or secondary follicles
  • abnormal vagina opening (MGI Ref ID J:76479)
    • vaginal opening is very small compared to wild-type
  • absent corpus luteum (MGI Ref ID J:76479)
    • no corpora lutea develops properly in ovary
  • decreased seminal gland weight (MGI Ref ID J:76479)
    • weight of gland is significantly lower than wild-type or heterozygotes
  • decreased testis weight (MGI Ref ID J:76479)
    • testis weight is significantly lower than in Lepob heterozygotes or Lep, Ppyr1 double null mice
    • testes weigh 0.19 g compared to 0.33 g in wild-type
  • female infertility (MGI Ref ID J:76479)
    • homozygous females produce no litters
  • male infertility (MGI Ref ID J:76479)
    • only one male tested was able to sire a litter
    • no males could produce offspring
  • prolonged diestrus (MGI Ref ID J:76479)
    • mice have diestrous-like swab until 9 weeks of age
  • prolonged estrous cycle (MGI Ref ID J:76479)
    • beginning at 9 weeks of age, estrous cycles last 11-15 days
  • prolonged estrus (MGI Ref ID J:76479)
    • beginning at 9 weeks of age, estrous-like cytology lasts 6-8 days
  • behavior/neurological phenotype
  • polyphagia (MGI Ref ID J:107169)
  • digestive/alimentary phenotype
  • abnormal intestine morphology (MGI Ref ID J:107169)
    • mice display intestinal hypertrophy compared to wild-type mice (intestine weight - 1.89 g vs 1.03 g in wild-type; intestine length 43 cm vs 33 cm in wild-type)
  • increased pancreas weight (MGI Ref ID J:107169)
    • 0.41 g vs 0.29 in wild-type
  • liver/biliary system phenotype
  • increased liver weight (MGI Ref ID J:107169)
    • 4.56 g vs 1.44 g in wild-type
  • renal/urinary system phenotype
  • increased kidney weight (MGI Ref ID J:107169)
    • 0.54 g vs 0.41 g in wild-type

Lepob/Lepob

        involves: 129/Sv * C57BL/6
  • homeostasis/metabolism phenotype
  • abnormal lipid level (MGI Ref ID J:121534)
    • sphingomeylin and antioxidant ethanolamine plasmlogen are markedly decreased
  • increased circulating insulin level (MGI Ref ID J:121534)
    • at 4 and 16 weeks of age
  • insulin resistance (MGI Ref ID J:121534)
    • at 16 weeks
  • endocrine/exocrine gland phenotype
  • abnormal pancreatic islet morphology (MGI Ref ID J:121534)
    • at 16 weeks, increased islet-to-pancreases volume ratios
    • at 16 weeks, islet insulin content is 30-fold greater than in Ppargtm1Avb Lepob homozygotes
    • enlarged pancreatic islets (MGI Ref ID J:121534)
    • increased pancreatic islet number (MGI Ref ID J:121534)
  • increased insulin secretion (MGI Ref ID J:121534)
    • at 16 weeks of age
  • behavior/neurological phenotype
  • hypoactivity (MGI Ref ID J:121534)
    • at 20 weeks, mice have decreased locomotor activity compared to wild-type
  • polyphagia (MGI Ref ID J:121534)
    • hyperphagic
  • growth/size phenotype
  • increased body weight (MGI Ref ID J:121534)
    • mice quickly become heavier and have significantly elevated body weights at 4 and 6 weeks of age in females and males, respectively
  • adipose tissue phenotype
  • increased percent body fat (MGI Ref ID J:121534)
    • 40% increase compared to wild-type at 20 weeks
  • liver/biliary system phenotype
  • hepatic steatosis (MGI Ref ID J:121534)
  • digestive/alimentary phenotype
  • abnormal pancreatic islet morphology (MGI Ref ID J:121534)
    • at 16 weeks, increased islet-to-pancreases volume ratios
    • at 16 weeks, islet insulin content is 30-fold greater than in Ppargtm1Avb Lepob homozygotes
    • enlarged pancreatic islets (MGI Ref ID J:121534)
    • increased pancreatic islet number (MGI Ref ID J:121534)
  • increased insulin secretion (MGI Ref ID J:121534)
    • at 16 weeks of age

Lepob/Lepob

        C57BL/6J-Lepob
  • homeostasis/metabolism phenotype
  • decreased circulating glucose level (MGI Ref ID J:129554)
    • when treated with AdipoR2-ASO, mice exhibit a decrease in plasma glucose level

Lepob/Lepob

        B6.V-Lepob/OlaHsd
  • digestive/alimentary phenotype
  • abnormal digestive system physiology (MGI Ref ID J:124815)
    • transepithelial resistance in the epithelium is reduced, indictive of a disrupted mucosal barrier function
  • abnormal intestinal epithelium morphology (MGI Ref ID J:124815)
    • reduced levels of occludin in intestinal sections
    • zonula occludens 1 has a discontinuous distribution
  • immune system phenotype
  • abnormal acute inflammation (MGI Ref ID J:124815)
    • higher levels of endotoxin are found in portal blood (entotoxemia)
    • increased susceptibility to endotoxin shock (MGI Ref ID J:124815)
      • increased succeptibility of hepatic stellate cells to LPS
  • abnormal chemokine secretion (MGI Ref ID J:124815)
    • increased release of monocyte chemo attractant protein by hepatic stellate cells
  • increased interleukin-6 secretion (MGI Ref ID J:124815)
    • increased release by hepatic stellate cells
  • liver inflammation (MGI Ref ID J:124815)
  • liver/biliary system phenotype
  • liver inflammation (MGI Ref ID J:124815)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
Hyperglycemia
Type 2 Diabetes (NIDDM)

Internal/Organ Research
Wound Healing (delayed/impaired)

Lepob related

Diabetes and Obesity Research
Hyperinsulinemia
Impaired Wound Healing
Insulin Resistance
Obesity With Diabetes

Endocrine Deficiency Research
Adipose Defects
Hypothalamus/Pituitary Defects
Pancreas Defects

Immunology and Inflammation Research
Immunodeficiency Associated with Other Defects

Internal/Organ Research
Adipose Defects

Metabolism Research

Mouse/Human Gene Homologs
obesity, severe, due to leptin deficiency (rare)

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol Lepob
Allele Name obese
Allele Type Spontaneous
Common Name(s) ob;
Strain of OriginSTOCK Mlph a Tgfa Cdh23 Ednrb
Gene Symbol and Name Lep, leptin
Chromosome 6
Gene Common Name(s) FLJ94114; OB; OBS; ob; obese;
General Note Homozygous obese mice are first recognizable at about 4 weeks of age. They increase in weight rapidly and may reach three times normal weight (J:13066). In addition to obesity, mutant mice exhibit hyperphagia; a diabetes-like syndrome of hyperglycemia, glucose intolerance, and elevated plasma insulin; subfertility; and increased hormone production from both pituitary and adrenal. They also have difficulty maintaining body temperature under cold conditions (J:7702).

The obesity is characterized by both an increased number of adipocytes and an increase in their size (J:7702); this is in contrast to other genetic obesities in the mouse in which increase in fat depots is due entirely to cell enlargement (J:5253, J:5765).

Hyperphagia may contribute tothe obesity. However, homozygotes gain excess weight and deposit excess fat even when restricted to a diet sufficient for normal lean mice, thus demonstrating an increased metabolic efficiency (J:6236). In parabiosis with normal mice, Lepob homozygotes eat less and lose weight; in parabiosis with Leprdb homozygotes, they cease eating completely and die of starvation. This is taken to mean that they have a normal response to a 'satiety' factor, presumably the leptin protein, but are unable to produce enough of it to maintain normal food intake (J:5401).

Hyperinsulinemia does not develop until after the increase in food intake and is probably the result of it (J:5759). It has been shown, however, that homozygous Lepob mice have an abnormally low threshold for stimulation of pancreatic islet insulin secretion (J:14402), even in very young animals before obesity develops (J:22634). As is the case with the diabetes mutant Leprdb, manifestation of the diabetic syndrome is strikingly dependent on genetic background. On a C57BL/6 background, Lepob homozygotes develop a well compensated diabetes with only temporary and moderate hyperglycemia, marked hyperinsulinemia, and enlarged islets of Langerhans. Onthe C57BLKS background, however, they become severely diabetic with regression of the islets and early death (J:5400).

Lepob homozygous mice have an impaired capacity for non-shivering thermogenesis which can be demonstrated at low temperatures as early as 10 days of age (J:12010). At 4 degrees C they rapidly become hypothermic and die within a few hours (J:5958). It has been suggested that a reduction in the energy requirement normally used for thermoregulatory heat production could be responsible for the increased metabolic efficiency noted above. That is unlikely to be the major cause of the thermoregulatory problems, however, since brief exposure of obese mice to 10 degrees C produces cold adaptation and allows indefinite survival at 4degrees C with maintenance of nearly normal body temperature (J:6756).

Coleman has suggested that the hyperinsulinemia of obese mice, which increases synthetic processes and decreases degradation, might spare the energy normally spent on tissue turnover and account at least in part for the increased efficiency (J:6756). Some contribution to the effect may also come from a low basal Na+,K+ATPase activity, shown to occur in muscle of 14-day old mutants (J:6182).

Heterozygotes (Lepob/+) have normal body weight, blood glucose, and plasma insulin, but can survive a prolonged fast longer than congenic wild-type controls, suggesting that increased metabolic efficiency is expressed to some extent in heterozygotes (J:159).

Female homozygotes are always sterile, although their ovaries respond to exogenous pituitary hormones. About 20% of male homozygotes may be transiently fertile, particularly if maintained on a restricted diet (J:7702).

Cloning of the Lep gene has made possible the production of recombinant leptin. Injection of this protein into Lepob homozygotes sharply reduces body weight, decreases food intake, and increases energy expenditure. There is no effect in diabetic Leprdb homozygotes, who are resistant to effects of the Lepob mutation. Normal mice also decrease food consumption and lose weight, with an accompanying loss in body fat (J:29161). Other investigators have obtained congruent results in normal and in Lepob mice (J:29162, J:29075); leptin also reduces food intake in fasted normal mice (J:28578). Leptin treatment effects on behavior of Lepob mice suggest a direct effect on neuronal networks (J:29160). Interactions of leptin with effects of hypothalamic lesions and of the Lepr gene indicate that Lep is upstream in the pathway of adipose tissue mass regulation (J:27422). Mutant leptin produced by the Lepob mutation fails to self-regulate production of leptin mRNA, which rises to a level 4 times that in normal mice. Lean mice when fasted decrease in leptin mRNA levels, but obese animals do not (J:29081).

There is a vast literature on the biochemical and physiological changes in Lepob mice, which has been reviewed by Herberg and Coleman (J:5759) and more recently by Charlton (J:7702). Many of the studies performed in adult mice may involve secondary effects of obesity rather than primary causes of it.

Increased blood levels of corticosterone occur in Lepob/Lepob mice, and most of the symptoms of the obese syndrome are ameliorated by excision of the adrenal glands. The hypothalamus-pituitary-adrenal axis is dysregulated, with hyperactivity of pituitary synthesis and secretion of adrenocorticotropic hormone (ACTH), as well as hyperresponsiveness of the adrenal cortex to ACTH (J:13151). Adrenal medullary activity, on the other hand, may be decreased; a diminished urinary excretion of epinephrine in obese homozygous mice indicates reduced medullary production, although this may be a secondary effect of the obesity (J:4033). A low serum level of the thyroid hormone triiodothyronine (T3) is also characteristic of obese homozygotes. Early treatment of these mice with T3 increases oxygen consumption and temperature while reducing body fat (J:22025). T3 treatment increases oxidative metabolism in muscle, but not in brown adipose tissue or in liver (J:22377).

Plasma triglyceride levels are elevated in mouse mutants considered models of non-insulin-dependent diabetes,including Lepob mutants. Cholesterol is also elevated, but the increase is primarily in high-density lipoprotein cholesterol (J:18161), so that atherosclerotic lesions are not increased (J:19043).

Molecular Note Sequencing of RT-PCR products revealed a nonsense mutation in codon 105 resulting from a C to T point mutation. The 16 kDa leptin protein, expressed predominantly in adipose tissue of normal mice, is missing from homozygous mutant mice (J:29081). [MGI Ref ID J:20512] [MGI Ref ID J:29081] [MGI Ref ID J:45748]

Genotyping

Genotyping Information

Genotyping Protocols

Lepob, PYRO, vers. 2
Lepob, REST, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Ewart-Toland A; Mounzih K; Qiu J; Chehab FF. 1999. Effect of the genetic background on the reproduction of leptin-deficient obese mice. Endocrinology 140(2):732-8. [PubMed: 9927300]  [MGI Ref ID J:52903]

Malik NM; Carter ND; Murray JF; Scaramuzzi RJ; Wilson CA; Stock MJ. 2001. Leptin requirement for conception, implantation, and gestation in the mouse. Endocrinology 142(12):5198-202. [PubMed: 11713215]  [MGI Ref ID J:94783]

Oler AT; Attie AD. 2008. A rapid, microplate SNP genotype assay for the leptinob allele. J Lipid Res 49(5):1126-9. [PubMed: 18272929]  [MGI Ref ID J:133040]

Additional References

Campfield LA; Smith FJ; Guisez Y; Devos R; Burn P. 1995. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks [see comments] Science 269(5223):546-9. [PubMed: 7624778]  [MGI Ref ID J:29160]

Charlton HM. 1984. Mouse mutants as models in endocrine research. Q J Exp Physiol 69(4):655-76. [PubMed: 6393185]  [MGI Ref ID J:7702]

Coleman DL. 1973. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 9(4):294-8. [PubMed: 4767369]  [MGI Ref ID J:5401]

Coleman DL. 1982. Thermogenesis in diabetes-obesity syndromes in mutant mice. Diabetologia 22(3):205-11. [PubMed: 7075918]  [MGI Ref ID J:6756]

Coleman DL; Hummel KP. 1973. The influence of genetic background on the expression of the obese (Ob) gene in the mouse. Diabetologia 9(4):287-93. [PubMed: 4588246]  [MGI Ref ID J:5400]

Erickson JC; Hollopeter G; Palmiter RD. 1996. Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274(5293):1704-7. [PubMed: 8939859]  [MGI Ref ID J:37106]

Halaas JL; Gajiwala KS; Maffei M; Cohen SL; Chait BT; Rabinowitz D; Lallone RL; Burley SK; Friedman JM. 1995. Weight-reducing effects of the plasma protein encoded by the obese gene [see comments] Science 269(5223):543-6. [PubMed: 7624777]  [MGI Ref ID J:29161]

Haluzik M; Colombo C; Gavrilova O; Chua S; Wolf N; Chen M; Stannard B; Dietz KR; Le Roith D; Reitman ML. 2004. Genetic background (C57BL/6J versus FVB/N) strongly influences the severity of diabetes and insulin resistance in ob/ob mice. Endocrinology 145(7):3258-64. [PubMed: 15059949]  [MGI Ref ID J:90742]

Herberg L; Coleman DL. 1977. Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism 26(1):59-99. [PubMed: 834144]  [MGI Ref ID J:5759]

Kaplan ML; Trout JR; Leveille GA. 1976. Adipocyte size distribution in ob/ob mice during preobese and obese phases of development. Proc Soc Exp Biol Med 153(3):476-82. [PubMed: 1013161]  [MGI Ref ID J:5765]

MacDougald OA; Hwang CS; Fan H; Lane MD. 1995. Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. Proc Natl Acad Sci U S A 92(20):9034-7. [PubMed: 7568067]  [MGI Ref ID J:29081]

Nishina PM; Lowe S; Wang J; Paigen B. 1994. Characterization of plasma lipids in genetically obese mice: the mutants obese, diabetes, fat, tubby, and lethal yellow. Metabolism 43(5):549-53. [PubMed: 8177042]  [MGI Ref ID J:18161]

Pelleymounter MA; Cullen MJ; Baker MB; Hecht R; Winters D; Boone T; Collins F. 1995. Effects of the obese gene product on body weight regulation in ob/ob mice [see comments] Science 269(5223):540-3. [PubMed: 7624776]  [MGI Ref ID J:29162]

Trayhurn P; James WP. 1978. Thermoregulation and non-shivering thermogenesis in the genetically obese (ob/ob) mouse. Pflugers Arch 373(2):189-93. [PubMed: 565045]  [MGI Ref ID J:5958]

Trayhurn P; Thurlby PL; James WP. 1977. Thermogenic defect in pre-obese ob/ob mice. Nature 266(5597):60-2. [PubMed: 840297]  [MGI Ref ID J:12010]

Zhang Y; Proenca R; Maffei M; Barone M; Leopold L; Friedman JM. 1994. Positional cloning of the mouse obese gene and its human homologue [published erratum appears in Nature 1995 Mar 30;374(6521):479] [see comments] Nature 372(6505):425-32. [PubMed: 7984236]  [MGI Ref ID J:20512]

Lepob related

Abe KC; Mori MA; Pesquero JB. 2007. Leptin deficiency leads to the regulation of kinin receptors expression in mice. Regul Pept 138(2-3):56-8. [PubMed: 17184856]  [MGI Ref ID J:137078]

Ablamunits V; Cohen Y; Brazee IB; Gaetz HP; Vinson C; Klebanov S. 2006. Susceptibility to Induced and Spontaneous Carcinogenesis Is Increased in Fatless A-ZIP/F-1 but not in Obese ob/ob Mice. Cancer Res 66(17):8897-902. [PubMed: 16951207]  [MGI Ref ID J:112412]

Ahima RS; Prabakaran D; Flier JS. 1998. Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function. J Clin Invest 101(5):1020-7. [PubMed: 9486972]  [MGI Ref ID J:118976]

Akpinar P; Kuwajima S; Krutzfeldt J; Stoffel M. 2005. Tmem27: a cleaved and shed plasma membrane protein that stimulates pancreatic beta cell proliferation. Cell Metab 2(6):385-97. [PubMed: 16330324]  [MGI Ref ID J:129667]

Albarado DC; McClaine J; Stephens JM; Mynatt RL; Ye J; Bannon AW; Richards WG; Butler AA. 2004. Impaired coordination of nutrient intake and substrate oxidation in melanocortin-4 receptor knockout mice. Endocrinology 145(1):243-52. [PubMed: 14551222]  [MGI Ref ID J:96671]

Alberts P; Nilsson C; Selen G; Engblom LO; Edling NH; Norling S; Klingstrom G; Larsson C; Forsgren M; Ashkzari M; Nilsson CE; Fiedler M; Bergqvist E; Ohman B; Bjorkstrand E; Abrahmsen LB. 2003. Selective inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains. Endocrinology 144(11):4755-62. [PubMed: 12960099]  [MGI Ref ID J:87239]

Allen DL; Cleary AS; Speaker KJ; Lindsay SF; Uyenishi J; Reed JM; Madden MC; Mehan RS. 2008. Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice. Am J Physiol Endocrinol Metab 294(5):E918-27. [PubMed: 18334608]  [MGI Ref ID J:135996]

Alon T; Friedman JM. 2006. Late-onset leanness in mice with targeted ablation of melanin concentrating hormone neurons. J Neurosci 26(2):389-97. [PubMed: 16407534]  [MGI Ref ID J:104264]

Aouadi M; Laurent K; Prot M; Le Marchand-Brustel Y; Binetruy B; Bost F. 2006. Inhibition of p38MAPK increases adipogenesis from embryonic to adult stages. Diabetes 55(2):281-9. [PubMed: 16443758]  [MGI Ref ID J:106432]

Ariyasu H; Takaya K; Hosoda H; Iwakura H; Ebihara K; Mori K; Ogawa Y; Hosoda K; Akamizu T; Kojima M; Kangawa K; Nakao K. 2002. Delayed short-term secretory regulation of ghrelin in obese animals: evidenced by a specific RIA for the active form of ghrelin. Endocrinology 143(9):3341-50. [PubMed: 12193546]  [MGI Ref ID J:81463]

Arvaniti K; Huang Q; Richard D. 2001. Effects of Leptin and Corticosterone on the Expression of Corticotropin-Releasing Hormone, Agouti-Related Protein, and Proopiomelanocortin in the Brain of ob/ob Mouse. Neuroendocrinology 73(4):227-36. [PubMed: 11340336]  [MGI Ref ID J:69137]

Asakawa A; Inui A; Ueno N; Makino S; Fujino MA; Kasuga M. 1999. Urocortin reduces food intake and gastric emptying in lean and ob/ob obese mice [see comments] Gastroenterology 116(6):1287-92. [PubMed: 10348810]  [MGI Ref ID J:57224]

Atkinson RD; Coenen KR; Plummer MR; Gruen ML; Hasty AH. 2008. Macrophage-derived apolipoprotein E ameliorates dyslipidemia and atherosclerosis in obese apolipoprotein E-deficient mice. Am J Physiol Endocrinol Metab 294(2):E284-90. [PubMed: 18029445]  [MGI Ref ID J:133332]

Back M; Sultan A; Ovchinnikova O; Hansson GK. 2007. 5-Lipoxygenase-activating protein: a potential link between innate and adaptive immunity in atherosclerosis and adipose tissue inflammation. Circ Res 100(7):946-9. [PubMed: 17379835]  [MGI Ref ID J:133901]

Baffy G; Zhang CY; Glickman JN; Lowell BB. 2002. Obesity-related fatty liver is unchanged in mice deficient for mitochondrial uncoupling protein 2. Hepatology 35(4):753-61. [PubMed: 11915020]  [MGI Ref ID J:106023]

Baldock PA; Allison S; McDonald MM; Sainsbury A; Enriquez RF; Little DG; Eisman JA; Gardiner EM; Herzog H. 2006. Hypothalamic regulation of cortical bone mass: opposing activity of Y2 receptor and leptin pathways. J Bone Miner Res 21(10):1600-7. [PubMed: 16995815]  [MGI Ref ID J:128105]

Baldock PA; Sainsbury A; Allison S; Lin EJ; Couzens M; Boey D; Enriquez R; During M; Herzog H; Gardiner EM. 2005. Hypothalamic control of bone formation: distinct actions of leptin and y2 receptor pathways. J Bone Miner Res 20(10):1851-7. [PubMed: 16160743]  [MGI Ref ID J:128137]

Bandsma RH; Grefhorst A; van Dijk TH; van der Sluijs FH; Hammer A; Reijngoud DJ; Kuipers F. 2004. Enhanced glucose cycling and suppressed de novo synthesis of glucose-6-phosphate result in a net unchanged hepatic glucose output in ob/ob mice. Diabetologia 47(11):2022-31. [PubMed: 15599701]  [MGI Ref ID J:107197]

Barouch LA; Berkowitz DE; Harrison RW; O'Donnell CP; Hare JM. 2003. Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation 108(6):754-9. [PubMed: 12885755]  [MGI Ref ID J:103063]

Barouch LA; Gao D; Chen L; Miller KL; Xu W; Phan AC; Kittleson MM; Minhas KM; Berkowitz DE; Wei C; Hare JM. 2006. Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survival in murine models of obesity. Circ Res 98(1):119-24. [PubMed: 16339484]  [MGI Ref ID J:118064]

Batra A; Pietsch J; Fedke I; Glauben R; Okur B; Stroh T; Zeitz M; Siegmund B. 2007. Leptin-dependent toll-like receptor expression and responsiveness in preadipocytes and adipocytes. Am J Pathol 170(6):1931-41. [PubMed: 17525261]  [MGI Ref ID J:122150]

Begin-Heick N. 1994. Liver beta-adrenergic receptors, G proteins, and adenylyl cyclase activity in obesity-diabetes syndromes. Am J Physiol 266(6 Pt 1):C1664-72. [PubMed: 8023896]  [MGI Ref ID J:18963]

Begriche K; Letteron P; Abbey-Toby A; Vadrot N; Robin MA; Bado A; Pessayre D; Fromenty B. 2008. Partial leptin deficiency favors diet-induced obesity and related metabolic disorders in mice. Am J Physiol Endocrinol Metab 294(5):E939-51. [PubMed: 18349116]  [MGI Ref ID J:136084]

Berk PD; Zhou S; Kiang C; Stump DD; Fan X; Bradbury MW. 1999. Selective up-regulation of fatty acid uptake by adipocytes characterizes both genetic and diet-induced obesity in rodents. J Biol Chem 274(40):28626-31. [PubMed: 10497230]  [MGI Ref ID J:57965]

Bhat GK; Hamm ML; Igietseme JU; Mann DR. 2003. Does leptin mediate the effect of photoperiod on immune function in mice? Biol Reprod 69(1):30-6. [PubMed: 12606383]  [MGI Ref ID J:84031]

Biddinger SB; Miyazaki M; Boucher J; Ntambi JM; Kahn CR. 2006. Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin and sterol regulatory element-binding protein-1c. Diabetes 55(7):2032-41. [PubMed: 16804073]  [MGI Ref ID J:111873]

Bina KG; Cincotta AH. 2000. Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releasing hormone, body weight gain, and hyperglycemia in ob/ob mice. Neuroendocrinology 71(1):68-78. [PubMed: 10644901]  [MGI Ref ID J:60273]

Bjorbaek C; Elmquist JK; Frantz JD; Shoelson SE; Flier JS. 1998. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell 1(4):619-25. [PubMed: 9660946]  [MGI Ref ID J:119803]

Bjursell M; Gerdin AK; Ploj K; Svensson D; Svensson L; Oscarsson J; Snaith M; Tornell J; Bohlooly-Y M. 2006. Melanin-concentrating hormone receptor 1 deficiency increases insulin sensitivity in obese leptin-deficient mice without affecting body weight. Diabetes 55(3):725-33. [PubMed: 16505236]  [MGI Ref ID J:106845]

Bobe G; Barrett KG; Mentor-Marcel RA; Saffiotti U; Young MR; Colburn NH; Albert PS; Bennink MR; Lanza E. 2008. Dietary cooked navy beans and their fractions attenuate colon carcinogenesis in azoxymethane-induced ob/ob mice. Nutr Cancer 60(3):373-81. [PubMed: 18444172]  [MGI Ref ID J:138534]

Bock T; Pakkenberg B; Buschard K. 2003. Increased islet volume but unchanged islet number in ob/ob mice. Diabetes 52(7):1716-22. [PubMed: 12829638]  [MGI Ref ID J:84295]

Bodary PF; Shen Y; Ohman M; Bahrou KL; Vargas FB; Cudney SS; Wickenheiser KJ; Myers MG Jr; Eitzman DT. 2007. Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy balance. Arterioscler Thromb Vasc Biol 27(1):70-6. [PubMed: 17095713]  [MGI Ref ID J:135034]

Borthwick EB; Burchell A; Coughtrie MW. 1995. Differential expression of hepatic oestrogen, phenol and dehydroepiandrosterone sulphotransferases in genetically obese diabetic (ob/ob) male and female mice. J Endocrinol 144(1):31-7. [PubMed: 7891022]  [MGI Ref ID J:22650]

Boston BA; Blaydon KM; Varnerin J; Cone RD. 1997. Independent and additive effects of central POMC and leptin pathways on murine obesity. Science 278(5343):1641-4. [PubMed: 9374468]  [MGI Ref ID J:44399]

Bouchard G; Johnson D; Carver T; Paigen B; Carey MC. 2002. Cholesterol gallstone formation in overweight mice establishes that obesity per se is not linked directly to cholelithiasis risk. J Lipid Res 43(7):1105-13. [PubMed: 12091495]  [MGI Ref ID J:88773]

Boudina S; Sena S; O'Neill BT; Tathireddy P; Young ME; Abel ED. 2005. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation 112(17):2686-95. [PubMed: 16246967]  [MGI Ref ID J:116841]

Bouhidel O; Pons S; Souktani R; Zini R; Berdeaux A; Ghaleh B. 2008. Myocardial ischemic postconditioning against ischemia-reperfusion is impaired in ob/ob mice. Am J Physiol Heart Circ Physiol 295(4):H1580-6. [PubMed: 18689499]  [MGI Ref ID J:141317]

Boundy VA; Cincotta AH. 2000. Hypothalamic adrenergic receptor changes in the metabolic syndrome of genetically obese (ob/ob) mice. Am J Physiol Regul Integr Comp Physiol 279(2):R505-14. [PubMed: 10938239]  [MGI Ref ID J:94672]

Bouret SG; Draper SJ; Simerly RB. 2004. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304(5667):108-10. [PubMed: 15064420]  [MGI Ref ID J:90241]

Breslow MJ; An Y; Berkowitz DE. 1997. Beta-3 adrenoceptor (beta-3AR) expression in leptin treated OB/OB mice. Life Sci 61(1):59-64. [PubMed: 9200670]  [MGI Ref ID J:41326]

Breslow MJ; Min-Lee K; Brown DR; Chacko VP; Palmer D; Berkowitz DE. 1999. Effect of leptin deficiency on metabolic rate in ob/ob mice. Am J Physiol 276(3 Pt 1):E443-9. [PubMed: 10070008]  [MGI Ref ID J:53833]

Brix AE; Elgavish A; Nagy TR; Gower BA; Rhead WJ; Wood PA. 2002. Evaluation of liver fatty acid oxidation in the leptin-deficient obese mouse. Mol Genet Metab 75(3):219-26. [PubMed: 11914033]  [MGI Ref ID J:94662]

Brun P; Castagliuolo I; Leo VD; Buda A; Pinzani M; Palu G; Martines D. 2007. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 292(2):G518-25. [PubMed: 17023554]  [MGI Ref ID J:124815]

Bruno RS; Dugan CE; Smyth JA; DiNatale DA; Koo SI. 2008. Green tea extract protects leptin-deficient, spontaneously obese mice from hepatic steatosis and injury. J Nutr 138(2):323-31. [PubMed: 18203899]  [MGI Ref ID J:133407]

Bruton JD; Katz A; Lannergren J; Abbate F; Westerblad H. 2002. Regulation of myoplasmic Ca(2+) in genetically obese (ob/ob) mouse single skeletal muscle fibres. Pflugers Arch 444(6):692-9. [PubMed: 12355168]  [MGI Ref ID J:106205]

Bunger L; Forsting J; McDonald KL; Horvat S; Duncan J; Hochscheid S; Baile CA; Hill WG; Speakman JR. 2003. Long-term divergent selection on fatness in mice indicates a regulation system independent of leptin production and reception. FASEB J 17(1):85-7. [PubMed: 12424222]  [MGI Ref ID J:118012]

Burcelin R; Kamohara S; Li J; Tannenbaum GS; Charron MJ; Friedman JM. 1999. Acute intravenous leptin infusion increases glucose turnover but not skeletal muscle glucose uptake in ob/ob mice. Diabetes 48(6):1264-9. [PubMed: 10342814]  [MGI Ref ID J:55776]

Busso N; So A; Chobaz-Peclat V; Morard C; Martinez-Soria E; Talabot-Ayer D; Gabay C. 2002. Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. J Immunol 168(2):875-82. [PubMed: 11777985]  [MGI Ref ID J:73743]

Butler AA; Marks DL; Fan W; Kuhn CM; Bartolome M; Cone RD. 2001. Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Nat Neurosci 4(6):605-11. [PubMed: 11369941]  [MGI Ref ID J:69814]

Campfield LA; Smith FJ; Guisez Y; Devos R; Burn P. 1995. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks [see comments] Science 269(5223):546-9. [PubMed: 7624778]  [MGI Ref ID J:29160]

Cani PD; Bibiloni R; Knauf C; Waget A; Neyrinck AM; Delzenne NM; Burcelin R. 2008. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57(6):1470-81. [PubMed: 18305141]  [MGI Ref ID J:136880]

Cao H; Maeda K; Gorgun CZ; Kim HJ; Park SY; Shulman GI; Kim JK; Hotamisligil GS. 2006. Regulation of metabolic responses by adipocyte/macrophage Fatty Acid-binding proteins in leptin-deficient mice. Diabetes 55(7):1915-22. [PubMed: 16804058]  [MGI Ref ID J:111878]

Cariou B; Capitaine N; Le Marcis V; Vega N; Bereziat V; Kergoat M; Laville M; Girard J; Vidal H; Burnol AF. 2004. Increased adipose tissue expression of Grb14 in several models of insulin resistance. FASEB J 18(9):965-7. [PubMed: 15059968]  [MGI Ref ID J:118114]

Cariou B; van Harmelen K; Duran-Sandoval D; van Dijk TH; Grefhorst A; Abdelkarim M; Caron S; Torpier G; Fruchart JC; Gonzalez FJ; Kuipers F; Staels B. 2006. The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem 281(16):11039-49. [PubMed: 16446356]  [MGI Ref ID J:110560]

Carley AN; Severson DL. 2005. Fatty acid metabolism is enhanced in type 2 diabetic hearts. Biochim Biophys Acta 1734(2):112-26. [PubMed: 15904868]  [MGI Ref ID J:99066]

Chakraborty S; Sachdev A; Salton SR; Chakraborty TR. 2008. Stereological analysis of estrogen receptor expression in the hypothalamic arcuate nucleus of ob/ob and agouti mice. Brain Res 1217:86-95. [PubMed: 18502406]  [MGI Ref ID J:138366]

Charlton HM. 1984. Mouse mutants as models in endocrine research. Q J Exp Physiol 69(4):655-76. [PubMed: 6393185]  [MGI Ref ID J:7702]

Cheema SK; Clandinin MT. 1996. Diet fat alters expression of genes for enzymes of lipogenesis in lean and obese mice. Biochim Biophys Acta 1299(3):284-8. [PubMed: 8597582]  [MGI Ref ID J:31603]

Chehab FF; Lim ME; Lu R. 1996. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 12(3):318-20. [PubMed: 8589726]  [MGI Ref ID J:31761]

Chen HC; Ladha Z; Farese RV Jr. 2002. Deficiency of acyl coenzyme a:diacylglycerol acyltransferase 1 increases leptin sensitivity in murine obesity models. Endocrinology 143(8):2893-8. [PubMed: 12130553]  [MGI Ref ID J:78337]

Chen HC; Smith SJ; Ladha Z; Jensen DR; Ferreira LD; Pulawa LK; McGuire JG; Pitas RE; Eckel RH; Farese RV Jr. 2002. Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1. J Clin Invest 109(8):1049-55. [PubMed: 11956242]  [MGI Ref ID J:76091]

Chen HL; Romsos DR. 1996. Dexamethasone rapidly increases hypothalamic neuropeptide Y secretion in adrenalectomized ob/ob mice. Am J Physiol 271(1 Pt 1):E151-8. [PubMed: 8760093]  [MGI Ref ID J:34501]

Chen HL; Romsos DR. 1994. Type II glucocorticoid receptors in the CNS regulate metabolism in ob/ob mice independent of protein synthesis. Am J Physiol 266(3 Pt 1):E427-32. [PubMed: 8166263]  [MGI Ref ID J:17505]

Chen J; Hui ST; Couto FM; Mungrue IN; Davis DB; Attie AD; Lusis AJ; Davis RA; Shalev A. 2008. Thioredoxin-interacting protein deficiency induces Akt/Bcl-xL signaling and pancreatic beta-cell mass and protects against diabetes. FASEB J 22(10):3581-94. [PubMed: 18552236]  [MGI Ref ID J:140264]

Chen J; Saxena G; Mungrue IN; Lusis AJ; Shalev A. 2008. Thioredoxin-interacting protein: a critical link between glucose toxicity and beta-cell apoptosis. Diabetes 57(4):938-44. [PubMed: 18171713]  [MGI Ref ID J:135529]

Chen NG; Romsos DR. 1995. Enhanced sensitivity of pancreatic islets from preobese 2-week-old ob/ob mice to neurohormonal stimulation of insulin secretion. Endocrinology 136(2):505-11. [PubMed: 7835283]  [MGI Ref ID J:22634]

Chen NG; Tassava TM; Romsos DR. 1993. Threshold for glucose-stimulated insulin secretion in pancreatic islets of genetically obese (ob/ob) mice is abnormally low. J Nutr 123(9):1567-74. [PubMed: 8360782]  [MGI Ref ID J:14402]

Chen Z; Newberry EP; Norris JY; Xie Y; Luo J; Kennedy SM; Davidson NO. 2008. ApoB100 is required for increased VLDL-triglyceride secretion by microsomal triglyceride transfer protein in ob/ob mice. J Lipid Res 49(9):2013-22. [PubMed: 18519977]  [MGI Ref ID J:139764]

Cheng A; Uetani N; Simoncic PD; Chaubey VP; Lee-Loy A; McGlade CJ; Kennedy BP; Tremblay ML. 2002. Attenuation of Leptin Action and Regulation of Obesity by Protein Tyrosine Phosphatase 1B. Dev Cell 2(4):497-503. [PubMed: 11970899]  [MGI Ref ID J:75969]

Chiu CH; Lin WD; Huang SY; Lee YH. 2004. Effect of a C/EBP gene replacement on mitochondrial biogenesis in fat cells. Genes Dev 18(16):1970-5. [PubMed: 15289464]  [MGI Ref ID J:91840]

Choo HJ; Kim JH; Kwon OB; Lee CS; Mun JY; Han SS; Yoon YS; Yoon G; Choi KM; Ko YG. 2006. Mitochondria are impaired in the adipocytes of type 2 diabetic mice. Diabetologia 49(4):784-91. [PubMed: 16501941]  [MGI Ref ID J:107887]

Christoffersen C; Bollano E; Lindegaard ML; Bartels ED; Goetze JP; Andersen CB; Nielsen LB. 2003. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology 144(8):3483-90. [PubMed: 12865329]  [MGI Ref ID J:84820]

Chua S Jr; Liu SM; Li Q; Yang L; Thassanapaff VT; Fisher P. 2002. Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB- Lepr (db)) and obese (DBA- Lep (ob)) mice. Diabetologia 45(7):976-90. [PubMed: 12136396]  [MGI Ref ID J:78850]

Chung WK; Belfi K; Chua M; Wiley J; Mackintosh R; Nicolson M; Boozer CN; Leibel RL. 1998. Heterozygosity for Lep(ob) or Lep(rdb) affects body composition and leptin homeostasis in adult mice. Am J Physiol 274(4 Pt 2):R985-90. [PubMed: 9575960]  [MGI Ref ID J:47168]

Clark EA; Shultz LD; Pollack SB. 1981. Mutations in mice that influence natural killer (NK) cell activity. Immunogenetics 12(5-6):601-13. [PubMed: 6971254]  [MGI Ref ID J:6485]

Claycombe K; King LE; Fraker PJ. 2008. A role for leptin in sustaining lymphopoiesis and myelopoiesis. Proc Natl Acad Sci U S A 105(6):2017-21. [PubMed: 18250302]  [MGI Ref ID J:131806]

Cleary MP; Bergstrom HM; Dodge TL; Getzin SC; Jacobson MK; Phillips FC. 2001. Restoration of fertility in young obese (Lep(ob) Lep(ob)) male mice with low dose recombinant mouse leptin treatment. Int J Obes Relat Metab Disord 25(1):95-7. [PubMed: 11244463]  [MGI Ref ID J:68694]

Cleary MP; Phillips FC; Getzin SC; Jacobson TL; Jacobson MK; Christensen TA; Juneja SC; Grande JP; Maihle NJ. 2003. Genetically obese MMTV-TGF-alpha/Lep(ob)Lep(ob) female mice do not develop mammary tumors. Breast Cancer Res Treat 77(3):205-15. [PubMed: 12602920]  [MGI Ref ID J:81933]

Clee SM; Nadler ST; Attie AD. 2005. Genetic and genomic studies of the BTBR ob/ob mouse model of type 2 diabetes. Am J Ther 12(6):491-8. [PubMed: 16280642]  [MGI Ref ID J:106121]

Clouthier DE; Comerford SA; Hammer RE. 1997. Hepatic fibrosis, glomerulosclerosis, and a lipodystrophy-like syndrome in PEPCK-TGF-beta1 transgenic mice. J Clin Invest 100(11):2697-713. [PubMed: 9389733]  [MGI Ref ID J:135399]

Coleman DL. 1973. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 9(4):294-8. [PubMed: 4767369]  [MGI Ref ID J:5401]

Coleman DL. 1982. Thermogenesis in diabetes-obesity syndromes in mutant mice. Diabetologia 22(3):205-11. [PubMed: 7075918]  [MGI Ref ID J:6756]

Coleman DL; Hummel KP. 1973. The influence of genetic background on the expression of the obese (Ob) gene in the mouse. Diabetologia 9(4):287-93. [PubMed: 4588246]  [MGI Ref ID J:5400]

Collin M; Hakansson-Ovesjo ML; Misane I; Ogren SO; Meister B. 2000. Decreased 5-HT transporter mRNA in neurons of the dorsal raphe nucleus and behavioral depression in the obese leptin-deficient ob/ob mouse. Brain Res Mol Brain Res 81(1-2):51-61. [PubMed: 11000478]  [MGI Ref ID J:109340]

Collins S; Daniel KW; Rohlfs EM; Ramkumar V; Taylor IL; Gettys TW. 1994. Impaired expression and functional activity of the beta 3- and beta 1-adrenergic receptors in adipose tissue of congenitally obese (C57BL/6J ob/ob) mice. Mol Endocrinol 8(4):518-27. [PubMed: 7914350]  [MGI Ref ID J:17709]

Collins S; Surwit RS. 1996. Pharmacologic manipulation of ob expression in a dietary model of obesity. J Biol Chem 271(16):9437-40. [PubMed: 8621612]  [MGI Ref ID J:33332]

Cope K; Risby T; Diehl AM. 2000. Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis. Gastroenterology 119(5):1340-7. [PubMed: 11054393]  [MGI Ref ID J:94789]

De Rosa V; Procaccini C; Cali G; Pirozzi G; Fontana S; Zappacosta S; La Cava A; Matarese G. 2007. A Key Role of Leptin in the Control of Regulatory T Cell Proliferation. Immunity 26(2):241-255. [PubMed: 17307705]  [MGI Ref ID J:118425]

Della-Fera MA; Choi YH; Hartzell DL; Duan J; Hamrick M; Baile CA. 2005. Sensitivity of ob/ob mice to leptin-induced adipose tissue apoptosis. Obes Res 13(9):1540-7. [PubMed: 16222056]  [MGI Ref ID J:114433]

Delporte ML; El Mkadem SA; Quisquater M; Brichard SM. 2004. Leptin treatment markedly increased plasma adiponectin but barely decreased plasma resistin of ob/ob mice. Am J Physiol Endocrinol Metab 287(3):E446-53. [PubMed: 15126241]  [MGI Ref ID J:95406]

Deng J; Hua K; Caveney EJ; Takahashi N; Harp JB. 2006. Protein inhibitor of activated STAT3 inhibits adipogenic gene expression. Biochem Biophys Res Commun 339(3):923-31. [PubMed: 16329991]  [MGI Ref ID J:104136]

Dickie MM; Lane PW. 1957. [Linkage of ob to L.G. XI] Mouse News Lett 17:52.  [MGI Ref ID J:159]

Dixon D; Horton J; Haseman JK; Talley F; Greenwell A; Nettesheim P; Hook GE; Maronpot RR. 1991. Histomorphology and ultrastructure of spontaneous pulmonary neoplasms in strain A mice. Exp Lung Res 17(2):131-55. [PubMed: 1646706]  [MGI Ref ID J:27691]

Dobrzyn A; Dobrzyn P; Lee SH; Miyazaki M; Cohen P; Asilmaz E; Hardie DG; Friedman JM; Ntambi JM. 2005. Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing beta-oxidation in skeletal muscle. Am J Physiol Endocrinol Metab 288(3):E599-607. [PubMed: 15562249]  [MGI Ref ID J:96073]

Dobrzyn P; Dobrzyn A; Miyazaki M; Cohen P; Asilmaz E; Hardie DG; Friedman JM; Ntambi JM. 2004. Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver. Proc Natl Acad Sci U S A 101(17):6409-14. [PubMed: 15096593]  [MGI Ref ID J:89545]

Dokmanovic-Chouinard M; Chung WK; Chevre JC; Watson E; Yonan J; Wiegand B; Bromberg Y; Wakae N; Wright CV; Overton J; Ghosh S; Sathe GM; Ammala CE; Brown KK; Ito R; LeDuc C; Solomon K; Fischer SG; Leibel RL. 2008. Positional cloning of 'Lisch-Like', a candidate modifier of susceptibility to type 2 diabetes in mice. PLoS Genet 4(7):e1000137. [PubMed: 18654634]  [MGI Ref ID J:138216]

Dong F; Zhang X; Yang X; Esberg LB; Yang H; Zhang Z; Culver B; Ren J. 2006. Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice. J Endocrinol 188(1):25-36. [PubMed: 16394172]  [MGI Ref ID J:104171]

Drel VR; Mashtalir N; Ilnytska O; Shin J; Li F; Lyzogubov VV; Obrosova IG. 2006. The leptin-deficient (ob/ob) mouse: a new animal model of peripheral neuropathy of type 2 diabetes and obesity. Diabetes 55(12):3335-43. [PubMed: 17130477]  [MGI Ref ID J:121015]

Dubuc PU. 1992. Interactions between insulin and glucocorticoids in the maintenance of genetic obesity. Am J Physiol 263(3 Pt 1):E550-5. [PubMed: 1415535]  [MGI Ref ID J:2939]

Ducy P; Amling M; Takeda S; Priemel M; Schilling AF; Beil FT; Shen J; Vinson C; Rueger JM; Karsenty G. 2000. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100(2):197-207. [PubMed: 10660043]  [MGI Ref ID J:60001]

El-Salhy M. 1998. Neuroendocrine peptides of the gastrointestinal tract of an animal model of human type 2 diabetes mellitus. Acta Diabetol 35(4):194-8. [PubMed: 9934817]  [MGI Ref ID J:55590]

Elefteriou F; Ahn JD; Takeda S; Starbuck M; Yang X; Liu X; Kondo H; Richards WG; Bannon TW; Noda M; Clement K; Vaisse C; Karsenty G. 2005. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434(7032):514-20. [PubMed: 15724149]  [MGI Ref ID J:97566]

Elefteriou F; Takeda S; Ebihara K; Magre J; Patano N; Kim CA; Ogawa Y; Liu X; Ware SM; Craigen WJ; Robert JJ; Vinson C; Nakao K; Capeau J; Karsenty G. 2004. Serum leptin level is a regulator of bone mass. Proc Natl Acad Sci U S A 101(9):3258-63. [PubMed: 14978271]  [MGI Ref ID J:88655]

Elinav E; Pappo O; Sklair-Levy M; Margalit M; Shibolet O; Gomori M; Alper R; Thalenfeld B; Engelhardt D; Rabbani E; Ilan Y. 2006. Adoptive transfer of regulatory NKT lymphocytes ameliorates non-alcoholic steatohepatitis and glucose intolerance in ob/ob mice and is associated with intrahepatic CD8 trapping. J Pathol 209(1):121-8. [PubMed: 16482497]  [MGI Ref ID J:107706]

Elinav E; Pappo O; Sklair-Levy M; Margalit M; Shibolet O; Gomori M; Alper R; Thalenfeld B; Engelhardt D; Rabbani E; Ilan Y. 2006. Amelioration of non-alcoholic steatohepatitis and glucose intolerance in ob/ob mice by oral immune regulation towards liver-extracted proteins is associated with elevated intrahepatic NKT lymphocytes and serum IL-10 levels. J Pathol 208(1):74-81. [PubMed: 16261527]  [MGI Ref ID J:104032]

Emanuelli B; Eberle D; Suzuki R; Kahn CR. 2008. Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance. Proc Natl Acad Sci U S A 105(9):3545-50. [PubMed: 18296638]  [MGI Ref ID J:132675]

Erickson JC; Hollopeter G; Palmiter RD. 1996. Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274(5293):1704-7. [PubMed: 8939859]  [MGI Ref ID J:37106]

Erickson JC; Hollopeter G; Palmiter RD. 1997. On raising energy expenditure in ob/ob mice Science 276(5315):1132-3. [PubMed: 9173544]  [MGI Ref ID J:40381]

Evans AA; Hughes S; Smith ME. 1995. Delta-opioid peptide receptors in muscles from obese diabetic and normal mice. Peptides 16(2):361-4. [PubMed: 7784267]  [MGI Ref ID J:24888]

Evans ZP; Ellett JD; Schmidt MG; Schnellmann RG; Chavin KD. 2008. Mitochondrial uncoupling protein-2 mediates steatotic liver injury following ischemia/reperfusion. J Biol Chem 283(13):8573-9. [PubMed: 18086675]  [MGI Ref ID J:135165]

Faggioni R; Fantuzzi G; Gabay C; Moser A; Dinarello CA; Feingold KR ; Grunfeld C. 1999. Leptin deficiency enhances sensitivity to endotoxin-induced lethality. Am J Physiol 276(1 Pt 2):R136-42. [PubMed: 9887187]  [MGI Ref ID J:52477]

Faggioni R; Fuller J; Moser A; Feingold KR; Grunfeld C. 1997. LPS-induced anorexia in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice. Am J Physiol 273(1 Pt 2):R181-6. [PubMed: 9249548]  [MGI Ref ID J:41966]

Faggioni R; Jones-Carson J; Reed DA; Dinarello CA; Feingold KR; Grunfeld C; Fantuzzi G. 2000. Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: role of tumor necrosis factor alpha and IL-18. Proc Natl Acad Sci U S A 97(5):2367-72. [PubMed: 10681432]  [MGI Ref ID J:60929]

Fan W; Boston BA; Kesterson RA; Hruby VJ; Cone RD. 1997. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome [see comments] Nature 385(6612):165-8. [PubMed: 8990120]  [MGI Ref ID J:37848]

Fauconnier J; Andersson DC; Zhang SJ; Lanner JT; Wibom R; Katz A; Bruton JD; Westerblad H. 2007. Effects of palmitate on Ca(2+) handling in adult control and ob/ob cardiomyocytes: impact of mitochondrial reactive oxygen species. Diabetes 56(4):1136-42. [PubMed: 17229941]  [MGI Ref ID J:122121]

Ferrante AW Jr; Thearle M; Liao T; Leibel RL. 2001. Effects of leptin deficiency and short-term repletion on hepatic gene expression in genetically obese mice. Diabetes 50(10):2268-78. [PubMed: 11574408]  [MGI Ref ID J:71975]

Ferrara CT; Wang P; Neto EC; Stevens RD; Bain JR; Wenner BR; Ilkayeva OR; Keller MP; Blasiole DA; Kendziorski C; Yandell BS; Newgard CB; Attie AD. 2008. Genetic networks of liver metabolism revealed by integration of metabolic and transcriptional profiling. PLoS Genet 4(3):e1000034. [PubMed: 18369453]  [MGI Ref ID J:134375]

Fleig SV; Choi SS; Yang L; Jung Y; Omenetti A; VanDongen HM; Huang J; Sicklick JK; Diehl AM. 2007. Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice. Lab Invest 87(12):1227-39. [PubMed: 17952094]  [MGI Ref ID J:128723]

Flowers JB; Rabaglia ME; Schueler KL; Flowers MT; Lan H; Keller MP; Ntambi JM; Attie AD. 2007. Loss of stearoyl-CoA desaturase-1 improves insulin sensitivity in lean mice but worsens diabetes in leptin-deficient obese mice. Diabetes 56(5):1228-39. [PubMed: 17369521]  [MGI Ref ID J:122081]

Frank S; Stallmeyer B; Kampfer H; Kolb N; Pfeilschifter J. 2000. Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair. J Clin Invest 106(4):501-9. [PubMed: 10953025]  [MGI Ref ID J:112351]

Fraser DC; Srivastava J; Woodward CJ; Simpson AE; Jones RB. 1998. A molecular investigation of the obese phenotype in the Aston University strain of ob/ob mice and the Japanese Kuo Kondo mice. Int J Obes Relat Metab Disord 22(2):193-4. [PubMed: 9504329]  [MGI Ref ID J:45748]

Fruhbeck G; Aguado M; Martinez JA. 1997. In vitro lipolytic effect of leptin on mouse adipocytes: evidence for a possible autocrine/paracrine role of leptin. Biochem Biophys Res Commun 240(3):590-4. [PubMed: 9398609]  [MGI Ref ID J:44321]

Fu L; John LM; Adams SH; Yu XX; Tomlinson E; Renz M; Williams PM; Soriano R; Corpuz R; Moffat B; Vandlen R; Simmons L; Foster J; Stephan JP; Tsai SP; Stewart TA. 2004. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Endocrinology 145(6):2594-603. [PubMed: 14976145]  [MGI Ref ID J:133073]

Fujimoto W; Shiuchi T; Miki T; Minokoshi Y; Takahashi Y; Takeuchi A; Kimura K; Saito M; Iwanaga T; Seino S. 2007. Dmbx1 is essential in agouti-related protein action. Proc Natl Acad Sci U S A 104(39):15514-9. [PubMed: 17873059]  [MGI Ref ID J:125193]

Fulton S; Pissios P; Manchon RP; Stiles L; Frank L; Pothos EN; Maratos-Flier E; Flier JS. 2006. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 51(6):811-22. [PubMed: 16982425]  [MGI Ref ID J:113646]

Gao D; Wei C; Chen L; Huang J; Yang S; Diehl AM. 2004. Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease. Am J Physiol Gastrointest Liver Physiol 287(5):G1070-7. [PubMed: 15231485]  [MGI Ref ID J:96152]

Gao H; Bryzgalova G; Hedman E; Khan A; Efendic S; Gustafsson JA; Dahlman-Wright K. 2006. Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3. Mol Endocrinol 20(6):1287-99. [PubMed: 16627594]  [MGI Ref ID J:108950]

Garris DR. 2004. Ultrastructural analysis of progressive endometrial hypercytolipidemia induced by obese (ob/ob) and diabetes (db/db) genotype mutations: structural basis of female reproductive tract involution. Tissue Cell 36(1):19-28. [PubMed: 14729450]  [MGI Ref ID J:102445]

Garris DR; Garris BL. 2004. Genomic modulation of diabetes (db/db) and obese (ob/ob) mutation-induced hypercytolipidemia: cytochemical basis of female reproductive tract involution. Cell Tissue Res 316(2):233-41. [PubMed: 15024641]  [MGI Ref ID J:105101]

Gautam D; Gavrilova O; Jeon J; Pack S; Jou W; Cui Y; Li JH; Wess J. 2006. Beneficial metabolic effects of M3 muscarinic acetylcholine receptor deficiency. Cell Metab 4(5):363-75. [PubMed: 17084710]  [MGI Ref ID J:129745]

Gavrilescu LC; Butcher BA; Del Rio L; Taylor GA; Denkers EY. 2004. STAT1 is essential for antimicrobial effector function but dispensable for gamma interferon production during Toxoplasma gondii infection. Infect Immun 72(3):1257-64. [PubMed: 14977926]  [MGI Ref ID J:88582]

Gavrilova O; Barr V; Marcus-Samuels B; Reitman M. 1997. Hyperleptinemia of pregnancy associated with the appearance of a circulating form of the leptin receptor. J Biol Chem 272(48):30546-51. [PubMed: 9374549]  [MGI Ref ID J:44331]

Gavrilova O; Leon LR; Marcus-Samuels B; Mason MM; Castle AL; Refetoff S; Vinson C; Reitman ML. 1999. Torpor in mice is induced by both leptin-dependent and -independent mechanisms. Proc Natl Acad Sci U S A 96(25):14623-8. [PubMed: 10588755]  [MGI Ref ID J:58946]

Getchell TV; Kwong K; Saunders CP; Stromberg AJ; Getchell ML. 2006. Leptin regulates olfactory-mediated behavior in ob/ob mice. Physiol Behav 87(5):848-56. [PubMed: 16549076]  [MGI Ref ID J:112820]

Gettys TW; Watson PM; Seger L; Padgett M; Taylor IL. 1997. Adrenalectomy after weaning restores beta3-adrenergic receptor expression in white adipocytes from C57BL/6J-ob/ob mice. Endocrinology 138(7):2697-704. [PubMed: 9202206]  [MGI Ref ID J:41996]

Gimeno RE; Dembski M; Weng X; Deng N; Shyjan AW; Gimeno CJ; Iris F; Ellis SJ; Woolf EA; Tartaglia LA. 1997. Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis. Diabetes 46(5):900-6. [PubMed: 9133562]  [MGI Ref ID J:40062]

Gloaguen I; Costa P; Demartis A; Lazzaro D; Di Marco A; Graziani R ; Paonessa G ; Chen F ; Rosenblum CI ; Van der Ploeg LH ; Cortese R ; Ciliberto G ; Laufer R. 1997. Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance. Proc Natl Acad Sci U S A 94(12):6456-61. [PubMed: 9177239]  [MGI Ref ID J:40976]

Goren I; Kampfer H; Muller E; Schiefelbein D; Pfeilschifter J; Frank S. 2006. Oncostatin M expression is functionally connected to neutrophils in the early inflammatory phase of skin repair: implications for normal and diabetes-impaired wounds. J Invest Dermatol 126(3):628-37. [PubMed: 16410783]  [MGI Ref ID J:106761]

Goren I; Kampfer H; Podda M; Pfeilschifter J; Frank S. 2003. Leptin and wound inflammation in diabetic ob/ob mice: differential regulation of neutrophil and macrophage influx and a potential role for the scab as a sink for inflammatory cells and mediators. Diabetes 52(11):2821-32. [PubMed: 14578302]  [MGI Ref ID J:86305]

Goren I; Muller E; Pfeilschifter J; Frank S. 2006. Severely impaired insulin signaling in chronic wounds of diabetic ob/ob mice: a potential role of tumor necrosis factor-alpha. Am J Pathol 168(3):765-77. [PubMed: 16507892]  [MGI Ref ID J:106484]

Goudriaan JR; Tacken PJ; Dahlmans VE; Gijbels MJ; van Dijk KW; Havekes LM; Jong MC. 2001. Protection from obesity in mice lacking the VLDL receptor. Arterioscler Thromb Vasc Biol 21(9):1488-93. [PubMed: 11557677]  [MGI Ref ID J:102939]

Gray SL; Nora ED; Grosse J; Manieri M; Stoeger T; Medina-Gomez G; Burling K; Wattler S; Russ A; Yeo GS; Chatterjee VK; O'Rahilly S; Voshol PJ; Cinti S; Vidal-Puig A. 2006. Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor gamma function (P465L PPARgamma) in mice. Diabetes 55(10):2669-77. [PubMed: 17003330]  [MGI Ref ID J:116568]

Grefhorst A; van Dijk TH; Hammer A; van der Sluijs FH; Havinga R; Havekes LM; Romijn JA; Groot PH; Reijngoud DJ; Kuipers F. 2005. Differential effects of pharmacological liver X receptor activation on hepatic and peripheral insulin sensitivity in lean and ob/ob mice. Am J Physiol Endocrinol Metab 289(5):E829-38. [PubMed: 15941783]  [MGI Ref ID J:102451]

Gruen ML; Plummer MR; Zhang W; Posey KA; Linton M; Fazio S; Hasty AH. 2005. Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I. J Lipid Res 46(9):2007-14. [PubMed: 15995171]  [MGI Ref ID J:100492]

Gundewar S; Calvert JW; Elrod JW; Lefer DJ. 2007. Cytoprotective effects of N,N,N-trimethylsphingosine during ischemia- reperfusion injury are lost in the setting of obesity and diabetes. Am J Physiol Heart Circ Physiol 293(4):H2462-71. [PubMed: 17630348]  [MGI Ref ID J:126117]

Guo KY; Halo P; Leibel RL; Zhang Y. 2004. Effects of obesity on the relationship of leptin mRNA expression and adipocyte size in anatomically distinct fat depots in mice. Am J Physiol Regul Integr Comp Physiol 287(1):R112-9. [PubMed: 15001430]  [MGI Ref ID J:109323]

Gupte A; Mora S. 2006. Activation of the Cbl insulin signaling pathway in cardiac muscle; dysregulation in obesity and diabetes. Biochem Biophys Res Commun 342(3):751-7. [PubMed: 16494846]  [MGI Ref ID J:106781]

Gustavsson N; Abedi G; Larsson-Nyren G; Lindstrom P. 2006. Timing of Ca2+ response in pancreatic beta-cells is related to mitochondrial mass. Biochem Biophys Res Commun 340(4):1119-24. [PubMed: 16414347]  [MGI Ref ID J:104995]

Hahm S; Fekete C; Mizuno TM; Windsor J; Yan H; Boozer CN; Lee C; Elmquist JK; Lechan RM; Mobbs CV; Salton SR. 2002. VGF is required for obesity induced by diet, gold thioglucose treatment, and agouti and is differentially regulated in pro-opiomelanocortin- and neuropeptide Y-containing arcuate neurons in response to fasting. J Neurosci 22(16):6929-38. [PubMed: 12177191]  [MGI Ref ID J:124244]

Hajri T; Hall AM; Jensen DR; Pietka TA; Drover VA; Tao H; Eckel R; Abumrad NA. 2007. CD36-facilitated fatty acid uptake inhibits leptin production and signaling in adipose tissue. Diabetes 56(7):1872-80. [PubMed: 17440173]  [MGI Ref ID J:126461]

Hakansson-Ovesjo ML; Collin M; Meister B. 2000. Down-regulated STAT3 messenger ribonucleic acid and STAT3 protein in the hypothalamic arcuate nucleus of the obese leptin-deficient (ob/ob) mouse Endocrinology 141(11):3946-55. [PubMed: 11089524]  [MGI Ref ID J:65568]

Halaas JL; Gajiwala KS; Maffei M; Cohen SL; Chait BT; Rabinowitz D; Lallone RL; Burley SK; Friedman JM. 1995. Weight-reducing effects of the plasma protein encoded by the obese gene [see comments] Science 269(5223):543-6. [PubMed: 7624777]  [MGI Ref ID J:29161]

Haller EW; Wittmers LE Jr; Haller IV; Regal RR. 1999. The obese gene is expressed in lean littermates of the genetically obese mouse (C57BL/6J ob/ob). Am J Physiol 276(4 Pt 1):E762-5. [PubMed: 10198314]  [MGI Ref ID J:54704]

Haluzik M; Colombo C; Gavrilova O; Chua S; Wolf N; Chen M; Stannard B; Dietz KR; Le Roith D; Reitman ML. 2004. Genetic background (C57BL/6J versus FVB/N) strongly influences the severity of diabetes and insulin resistance in ob/ob mice. Endocrinology 145(7):3258-64. [PubMed: 15059949]  [MGI Ref ID J:90742]

Hamm ML; Bhat GK; Thompson WE; Mann DR. 2004. Folliculogenesis is impaired and granulosa cell apoptosis is increased in leptin-deficient mice. Biol Reprod 71(1):66-72. [PubMed: 14985253]  [MGI Ref ID J:91001]

Hamrick MW; Pennington C; Newton D; Xie D; Isales C. 2004. Leptin deficiency produces contrasting phenotypes in bones of the limb and spine. Bone 34(3):376-83. [PubMed: 15003785]  [MGI Ref ID