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Strain Name:

BKS.Cg-m +/+ Leprdb/J

Stock Number:

000642

Availability:

Level 2

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General Terms and Conditions

Former Name      BKS.Cg-m+/+Leprdb/J    (Changed: 25-JAN-07 )
      C57BLKS-m Leprdb    (Changed: 17-NOV-05 )
Genes & Alleles   Lepr;   Leprdb;   m;

Product Information

Strain Details

Type JAX® GEMM® Strain - Coisogenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Congenic
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Spontaneous Mutation
Specieslaboratory mouse
Background Strain C57BLKS/J
Donor Strain Leprdb, C57BLKS; m, DBA/J
H2 Haplotyped
GenerationF113 (03-JAN-08)

Appearance
Leprdb: black, fat
Related Genotype: a/a + Leprdb/+ Leprdb

m Leprdb: black, lean
Related Genotype: a/a m +/+ Leprdb

m: misty (grey), lean
Related Genotype: a/a m +/m +

Important Note
This strain is maintained with m and Leprdb in repulsion. Although these genes are tightly linked, there is a small possibility of recombination. The heterozygotes we distribute are presumed to be non-recombinant, but are untested.

Strain Description
Mice homozygous for the diabetes spontaneous mutation (Leprdb) become identifiably obese around 3 to 4 weeks of age. Elevations of plasma insulin begin at 10 to 14 days of age and of blood sugar at 4 to 8 weeks. Homozygous mutant mice are polyphagic, polydipsic, and polyuric. The course of the disease is markedly influenced by genetic background. A number of features are observed on the C57BLKS background, including an uncontrolled rise in blood sugar, severe depletion of the insulin-producing beta-cells of the pancreatic islets, and death by 10 months of age. Exogenous insulin fails to control blood glucose levels and gluconeogenic enzyme activity increases. Peripheral neuropathy and myocardial disease are seen in C57BLKS-Leprdb homozygotes. Wound healing is delayed, and metabolic efficiency is increased. Female homozygotes exhibit decreased uterine and ovarian weights, decreased ovarian hormone production and hypercytolipidemia in follicular granulosa and endometrial epithelial tissue layers (Garris et al., 2004, Garris et al., 2004).

Although normal in body weight, blood glucose, and plasma insulin, heterozygotes (Leprdb/+) also have increased metabolic efficiency and can survive a prolonged fast longer than controls. Experiments involving destruction of the ventromedial nucleus of the hypothalamus suggest that Leprdb may cause a defect in the hypothalamus. Steroid sulfotransferase enzymes, aberrantly expressed in diabetic mice, interact with the Leprdb mutation as modifiers of gender differences in obesity-induced diabetes susceptibility. Because of the sterility of Leprdb homozygotes, the misty (m) mutation has been incorporated into stocks for maintenance of the diabetes mutation. The repulsion double heterozygote (m +/+ Leprdb) facilitates identification of heterozygotes for breeding, while the coupling double heterozygote, (m Leprdb/+ +) allows identification of homozygotes before the onset of clinical symptoms.

The recessive misty mutation causes a mild dilution of coat color and on certain backgrounds a white tail tip often accompanied by a belly spot. Melanocytes from m/m mice have a highly dendritic shape, show deficient proliferation in culture and have much more melanin content. Fewer melanoblasts are found in primary cultures from m/m mice than from wildtype controls. Between two and five weeks of age, m/m mice are smaller than controls. At 35 days of age they are shorter, weigh 15% less on average, and have less inguinal adipose mass than controls. Misty homozygotes completely lack brown fat. Although platelet count, seratonin content and ATP content are normal, m/m homozygotes have an increased bleed time and reduced platelet ADP levels.(Woolley 1941 and 1945; Truett et al 1998; Sviderskaya et al 1998.)

Related Disease (OMIM) Terms

Diabetes Mellitus, Noninsulin-Dependent; NIDDM
Mammalian Phenotype Terms assigned by genotype

Leprdb/Lepr+

        involves: C57BLKS/J
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis (J:71934)
    • abnormal circulating insulin level (J:71934)
      • 2.2X increase in fasting insulin during pregnancy compared to a 3X increase in controls
      • leptin treatment results in a 14% reduction in insulin levels compared to a 45% reduction in controls
    • impaired glucose tolerance (J:71934)
      • profound glucose intolerance during pregnancy
      • glucose levels 41% higher in a glucose tolerance test at 30 and at 60 minute time points
      • 45-55% higher glucose levels after a glucose challenge but dramatically improved by leptin treatment and glucose levels reduced 33 and 30% in glucose tolerance tests at 30 and 60 minute time points
    • increased circulating glucose level (J:71934)
      • fasting glucose levels elevated 25% during pregnancy
  • abnormal hormone level (J:71934)
    • elevated placental leptin levels in pregnant females
    • abnormal circulating insulin level (J:71934)
      • 2.2X increase in fasting insulin during pregnancy compared to a 3X increase in controls
      • leptin treatment results in a 14% reduction in insulin levels compared to a 45% reduction in controls
  • behavior/neurological phenotype
  • increased eating behavior (J:71934)
    • food intake 11% greater than controls during pregnancy
    • leptin treatment suppresses food intake to near control levels
  • growth/size phenotype
  • increased weight gain (J:71934)
    • 33% greater maternal weight gain
    • maternal body weight at term 24% greater than controls
    • birth weights significantly heavier than controls and unaffected by maternal leptin treatment unlike controls where maternal leptin treatment causes a decrease in birth weights
  • adipose tissue phenotype
  • increased adipose tissue amount (J:71934)
    • 20% greater adipose tissue mass during pregnancy than in controls

Leprdb/Lepr+

        BKS.Cg-m +/+ Leprdb/J
  • life span-post-weaning/aging
  • extended life span (J:6081)
    • increased survival when totally deprived of food than wild type controls
    • survival when deprived of food is longer rhan when in a C57BL/6 background

Leprdb/Leprdb

        involves: C57BLKS/J
  • homeostasis/metabolism phenotype
  • abnormal body temperature regulation (J:89242)
    • mutants become hypothermic after a 12 hour fast
    • mutants housed at 4 degrees C for 3.5 hours cannot maintain their body temperature like wild type and drop about 1 degree in body temperature every 30 min until they reach 34 degrees C, at which point they stabilize this temperature, indicating decreased sympathetic activity
  • abnormal glucose homeostasis (J:80996)
    • decreased circulating glucose level (J:117919)
      • mice treated with adenovirus expressing Adipor1 (1.5-fold increase in liver expression), show decreased plasma glucose compared to wild type
      • mice treated with an adenovirus expressing Adipor2 (5-fold increase in liver expression), show decreased plasma glucose compared to wild type
    • decreased circulating insulin level (J:117919)
      • mice treated with an adenovirus expressing Adipor 2 show improved glucose resistance and decreased plasma insulin level
    • impaired glucose tolerance (J:89242)
    • increased circulating glucose level (J:5010)
      • plasma fasting glucose is increased
      • hyperglycemia (J:117919)
        • diabetes is improved after treatment with an adenovirus expressing Adipor1 or Adipor2
    • increased circulating insulin level (J:5010)
      • fasting insulin is increased
    • insulin resistance (J:117919)
      • mice treated with an adenovirus expressing Adipor1 or Adipor 2 show improved insulin resistance
  • increased circulating corticosterone level (J:89242)
  • increased circulating leptin level (J:89242)
  • proteinuria (J:5257)
    • in females when compared to female controls
    • levels of protein in urine similar in males and females but levels in males lower than in male controls
  • growth/size phenotype
  • decreased body length (J:89242)
    • mutants are about 5% shorter than controls
  • increased body weight (J:5010)
    • by four weeks of age
  • reproductive system phenotype
  • abnormal uterus morphology (J:80996)
    • abnormal endometrium morphology (J:80996)
      • increased volume and density of lipid inclusion vacuoles
      • basal membrane of epithelial cells displays a folded contour at locations where lipid accumulates
      • tissue norepinephrin levels elevated by 4 weeks of age and remain elevated
    • decreased uterus weight (J:80996)
      • decreased relative to controls by 4 weeks of age
      • 1/3 normal tissue weight by 12 weeks
  • vision/eye phenotype
  • abnormal intraocular pressure (J:82879)
    • modest but significant elevation of intraocular pressure
  • behavior/neurological phenotype
  • abnormal conditioned taste aversion behavior (J:85127)
    • aversion response is more strongly generalized from saccharin to sucrose
    • lower aversion threshold for sucrose than in controls
    • recovery from conditioned taste aversion is more rapid than in controls
  • polydipsia (J:5010)
  • polyphagia (J:5010)
  • renal/urinary system phenotype
  • abnormal calyx morphology (J:5257)
    • calyceal dilation eventually develops
  • abnormal kidney papilla morphology (J:5257)
    • eventually becomes flattened
  • abnormal renal glomerulus morphology (J:30970)
    • large quantites if immunoglobulin and complement are found in the mesangium
    • basement membrane becomes thickened with age
  • polyuria (J:5010)
  • proteinuria (J:5257)
    • in females when compared to female controls
    • levels of protein in urine similar in males and females but levels in males lower than in male controls
  • immune system phenotype
  • increased susceptibility to autoimmune diabetes (J:7005)
    • T cells from homozygous mice but not those from heterozygous mice suppressed the beta cell response to glucose + theophylline
  • endocrine/exocrine gland phenotype
  • abnormal hypothalamus physiology (J:1325)
    • hypothalamic uptake of norepinephrine is decreased in males
  • nervous system phenotype
  • abnormal hypothalamus physiology (J:1325)
    • hypothalamic uptake of norepinephrine is decreased in males
  • adipose tissue phenotype
  • increased adipose tissue amount (J:89242)
    • increase in total fat content

Leprdb/Leprdb

        C57BLKS/J
  • behavior/neurological phenotype
  • polyphagia (J:96047)
  • digestive/alimentary phenotype
  • abnormal islet of Langerhans morphology (J:96047)
    • islet mass and density are significantly increased compared to wild type mice
    • abnormal pancreatic beta cell morphology (J:96047)
      • individual beta cell size is increased
  • endocrine/exocrine gland phenotype
  • abnormal islet of Langerhans morphology (J:96047)
    • islet mass and density are significantly increased compared to wild type mice
    • abnormal pancreatic beta cell morphology (J:96047)
      • individual beta cell size is increased
  • growth/size phenotype
  • increased body weight (J:106597)
    • overweight by 4 weeks of age
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis (J:107138)
    • diabetic phenotype appears earlier in males than in females
    • hyperglycemia (J:104790)
      • by 8 weeks
    • increased circulating insulin level (J:104790)
      • hyperinsulinemia by 8 weeks
  • abnormal metabolism (J:107138)
    • carbohydrate oxidation becomes reduced
    • palmitate oxidation is elevated
  • altered response to myocardial infarction (J:104790)
    • homozygotes subjected to 45 min of ischemia display an increase in diastolic dimensions, significant dilatation of left ventricular end-systolic dimensions, a 30% reduction in fractional shortening, and an increase in cardiac hypertrophy, 28 days postreperfusion, indicating decreased tolerance to myocardial infarction
  • decreased body temperature (J:96047)
  • hyperlipidemia (J:96047)
  • incleased glycosylated hemoglobin level (J:104790)
    • significant increase in the percentage of plasma glycosylated hemoglobin
  • increased circulating free fatty acid level (J:106871)
  • cardiovascular system phenotype
  • abnormal cardiac muscle morphology (J:107138)
    • myocardial triacylglycerol content 2X that of controls at 10-18 weeks of age
  • abnormal cardiovascular system physiology (J:107138)
    • at low fatty acid supply, hearts consume 86% more oxygen (MVO2) for noncontractile purposes compared with control hearts and a further increase in fatty acid supply has no effect on the already elevated unloaded MVO2, indicating reduced cardiac efficiency in unloaded hearts
    • abnormal blood circulation (J:107138)
      • reduced aortic flow
      • cardiac ischemia (J:107138)
        • reduced recovery of mechanical function after 13 minutes of ischemia and reperfusion
      • decreased cardiac output (J:107138)
        • cardiac output is reduced in fatty acid perfused hearts
    • altered response to myocardial infarction (J:104790)
      • homozygotes subjected to 45 min of ischemia display an increase in diastolic dimensions, significant dilatation of left ventricular end-systolic dimensions, a 30% reduction in fractional shortening, and an increase in cardiac hypertrophy, 28 days postreperfusion, indicating decreased tolerance to myocardial infarction
    • decreased cardiac muscle contractility (J:106871)
      • hearts show a significant increase in the slope of the MVO2-PVA (pressure volume area) regression line after elevation of fatty acids, suggesting a reduction in contractile efficiency
    • decreased heart rate (J:107138)
      • intrinsic heart rates are reduced at all workloads
    • decreased systolic blood pressure (J:107138)
      • decreased peak systolic pressure
      • decreased peak systolic pressure X cardiac output
      • decreased peak systolic pressure X heart rate
    • increased left ventricle diastolic pressure (J:106871)
      • hearts show a significant increase in the slope of the MVO2-PVA (pressure volume area) regression line after elevation of fatty acids, suggesting a reduction in contractile efficiency
  • hematopoietic system phenotype
  • incleased glycosylated hemoglobin level (J:104790)
    • significant increase in the percentage of plasma glycosylated hemoglobin
  • life span-post-weaning/aging
  • abnormal induced morbidity/mortality (J:104790)
    • homozygotes subjected to 30, 45, and 60 min of left coronary artery ischemia-reperfusion exhibit survival rates of 71%, 53%, and 18%, respectively, at 24 h after reperfusion, much lower than in controls
    • homozygotes subjected to 30 and 45 min of left coronary artery occlusion show survival rates of 58% and 44%, respectively, at 28 days after reperfusion, compared to 100% and 88% in controls
  • cellular phenotype
  • abnormal aerobic energy metabolism (J:106871)
    • elevation of fatty acids in perfused hearts causes an increase in fatty acid oxidation combined with a reduction in glucose oxidation rates
    • state 3 respiration is elevated in cardiac mitochondria incubated with palmitoyl-carnitine but not with pyruvate
  • muscle phenotype
  • abnormal cardiac muscle morphology (J:107138)
    • myocardial triacylglycerol content 2X that of controls at 10-18 weeks of age
  • decreased cardiac muscle contractility (J:106871)
    • hearts show a significant increase in the slope of the MVO2-PVA (pressure volume area) regression line after elevation of fatty acids, suggesting a reduction in contractile efficiency
  • increased vascular smooth muscle contraction (J:106597)
    • hypercontractility of smooth muscle in aortic strips due to either phenylephrine or serotonin
    • hypercontractility corrollated with the levels of obesity, hyperglycemia, and hyperinsulinemia
    • maximal contractions increase with age rather than decrease as in controls

Leprdb/Leprdb

        BKS.Cg-m +/+ Leprdb/J
  • homeostasis/metabolism phenotype
  • abnormal circulating glucose level (J:43162)
    • decreased circulating glucose level (J:43162)
      • brain derived neurotrophic factor (BDNF) causes a drop in blood glucose relative to controls 8 weeks after treatment
      • affect of BDNF on blood glucose becomes progressively less as mice age
      • neurotrophin 3 also causes a drop in blood glucose but the glucose levels return to normal by 24 hours after treatment
      • glucose levels are reduced at all times tested when mice are placed on feeding restriction during the dark phase
    • increased circulating glucose level (J:6323)
      • blood glucose shows a progressive increase from 5 through 33 weeks
  • abnormal circulating lipid level (J:18161)
    • plasma lipid levels differ between young and old mutants unlike on the C57BL/6J background where levels are similar at both ages; 14-month old mice have lower triglycerides, HDL cholesterol and combined VLDL + LDL cholesterol levels than 14-week old mice, but have significantly higher plasma triglyceride levels
    • abnormal circulating cholesterol level (J:18161)
      • increased circulating cholesterol level (J:18161)
        • fasting plasma total cholesterol concentration is increased 2 fold over controls
        • increased circulating HDL cholesterol level (J:18161)
        • increased circulating LDL cholesterol level (J:18161)
        • increased circulating VLDL cholesterol level (J:18161)
    • decreased circulating triglyceride level (J:91813)
      • triglyceride levels are reduced at all times tested when mice are placed on feeding restriction during the dark phase
    • increased circulating triglyceride level (J:18161)
      • triglyceride levels are elevated 1.5- to 2-fold
  • decreased albumin excretion (J:82491)
    • mutants treated with sRAGE do not show the increased albumin excretion seen in untreated mutants (0.11 ug albumin/ug creatinine vs 0.20 ug albumin/ ug creatinine); levels are not significantly different from control animals (0.08 ug albumin/ ug creatinine)
  • decreased circulating insulin level (J:43162)
    • BDNF causes a 50% reduction in plasma insulin relative to controls
    • morning insulin levels lowered when feeding is restricted during the dark phase
  • improved glucose tolerance (J:43162)
    • BDNF treatment causes a lower blood glucose level response in a glucose tolerance test
  • growth/size phenotype
  • obese (J:6323)
    • become progressively obese starting at 5 weeks of age
    • weight reaches 2.5X that of control mice by 3 months of age
  • weight loss (J:91813)
    • body weight drops after 6 days on feeding restriction during the dark phase
  • renal/urinary system phenotype
  • decreased albumin excretion (J:82491)
    • mutants treated with sRAGE do not show the increased albumin excretion seen in untreated mutants (0.11 ug albumin/ug creatinine vs 0.20 ug albumin/ ug creatinine); levels are not significantly different from control animals (0.08 ug albumin/ ug creatinine)
  • increased creatinine clearance (J:82491)
    • male mutants treated with sRAGE to achieve RAGE blockade display increased creatinine clearance (~5.1 ml/hour/100 x g body weight) compared to PBS-treated mutants (~3 ml/hour/100 x g body weight), approaching wild type levels (6.7 ml/hour/100 x g body weight)
  • nervous system phenotype
  • abnormal CNS synaptic transmission (J:109401)
    • absent long term depression (J:109401)
      • CA1 hippocampal slices indicate no long term depression on recordings of excitatory post-synaptic potentials
    • reduced long term potentiation (J:109401)
      • CA1 hippocampal slices indicate brief post tetanic potentiation but no long term potentiation on recordings of excitatory post-synaptic potentials
  • abnormal nerve conduction (J:6323)
    • motor nerve conductance significantly lower than controls from 7 weeks of age onward
    • velocity returns to and is maintained at prediabetic levels by 15 weeks of age whereas control mice show a continuous increase in velocity
    • insulin treatment results in improved conductance but only for the duration of treatment and control levels of conductance are never restored
    • no conductance improvement is seen in mice over 23 weeks in age due to insulin treatment
  • abnormal nervous system morphology (J:6323)
    • abnormal axon morphology (J:6323)
      • non significant shift toward smaller fiber diameter at 15 weeks of age
      • significantly shifted to smaller diameter fibers by 25 weeks in ventral roots, dorsal roots, sural nerve
      • smaller diameter nerve fibers in peroneal, phrenic and vagus nerves at 25 weeks but not significant
      • small numbers of very large unmyelinated fibers (up to 1.6 micrometers)
      • shift of unmyelinated fibers to smaller diameters
      • abnormal myelin sheath morphology (J:6323)
        • number of myelin lamellae relative to nerve diameter is increased
    • abnormal axon outgrowth (J:112680)
      • axonal growth cone extension fails to occur for neurons treated in culture with 100ng/ml of leptin
    • decreased motor neuron number (J:6323)
      • myelinated fibers reduced in numbers at 25 weeks in the sural nerve
      • unmyelinated fibers reduced in numbers at 25 weeks in the vagus nerve
      • myelinated fiber density increases in most nerves (not the peroneal and phrenic nerves)
      • unmyelinated fiber density increase in the sural, peroneal, and vagus nerves
  • behavior/neurological phenotype
  • abnormal circadian rhythm (J:91813)
    • daily locomotor pattern becomes attenuated in 6-8 week old mice but rhythmicity is retained
    • daily locomotor activity rhythmicity severely diminished at 13-14 weeks, 75% fail to show significant rhythmicity
    • daily locomotor rhythmicity restored by feeding restriction during dark phase
  • abnormal food intake (J:43162)
    • food intake is about 60% of control level
  • abnormal learning/memory/conditioning (J:109401)
    • abnormal spatial learning (J:109401)
      • longer swimming distances than control mice in a Morris water maze test
    • abnormal spatial reference memory (J:109401)
      • cross the original platform location less frequently than do controls in a Morris water maze test
  • vision/eye phenotype
  • abnormal eye electrophysiology (J:103714)
    • prolonged latency of the b-wave in the retina
    • delays in oscillatory potentials 1, 2, 3 although only the delay in "OP1" is significant
  • digestive/alimentary phenotype
  • increased glucagon secretion (J:6264)
    • increased secreation of glucagon by pancreatic cells in culture
  • endocrine/exocrine gland phenotype
  • increased glucagon secretion (J:6264)
    • increased secreation of glucagon by pancreatic cells in culture
  • cardiovascular system phenotype
  • abnormal myocardial fiber morphology (J:6115)
    • presence of many lipid droplets
    • dense bodies present in places normally occupied by mitochondria
    • disrupted sarcomeres sometimes
  • abnormal vascular development (J:6115)
    • dense bodies found in the smooth muscle of intramyocardial arteries
  • muscle phenotype
  • abnormal myocardial fiber morphology (J:6115)
    • presence of many lipid droplets
    • dense bodies present in places normally occupied by mitochondria
    • disrupted sarcomeres sometimes

Leprdb/Leprdb

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

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

Leprdb/Lepr+

        B6.Cg-m +/+ Leprdb/J
  • growth/size phenotype
  • increased body weight (J:82334)
    • slight but significant increase in body weight compared to wild type mice
  • life span-post-weaning/aging
  • extended life span (J:6081)
    • increased survival when totally deprived of food than wild type controls
    • survival when deprived of food is not as long as when in a C57BLKsS background

Leprdb/Leprdb

        FVB.BKS-Leprdb
  • growth/size phenotype
  • obese (J:78850)
    • mice of both sexes are obese
  • homeostasis/metabolism phenotype
  • abnormal circulating glucose level (J:78850)
    • after a 2-day fast on refeeding with carbohydrate-free diet, female obese mice show a rise in glucose
    • hyperglycemia (J:78850)
      • obese mice have a prolonged period of hyperglycemia compared to obese B6.BKS-Leprdb mice where glucose levels rarely exceed 250 mg/dl
      • fasting mice are hyperglycemic at 3 months of age, while obese B6.BKS-Leprdb fasted mice are euglycemic
      • levels increase from 5 to 7 months in obese females to ~500 ng/ml, significantly higher than the males (~40 ng/ml) or obese B6.BKS-Leprdb females (~50 ng/ml)
  • impaired glucose tolerance (J:78850)
    • at 7 months of age obese males are severely glucose intolerant with glucose levels of >400 mg/dl 90 minutes after glucose load compared to obese B6.BKS-Leprdb mice clear glucose load by 90 min
    • obese mice show a rapid increase of blood glucose above 400 mg/dl with diminished rate of glucose clearance
  • increased circulating insulin level (J:78850)
    • at 3 months of age, females show a trend toward higher insulin levels compared to obese B6.BKS-Leprdb females; at 5-7 months insulin levels (~500 ng/ml) are ~10-fold higher than levels in obese female obese B6.BKS-Leprdb mice (~50 ng/ml)
  • insulin resistance (J:78850)
    • at 7 months of age, 3U/kg of insulin does not alter circulating glucose levels, while in B6.BKS-Lepr mice, glucose decreases by 50% by 40 minutes; 12U/kg insulin does not cause a decrease in glucose in obese female mice on the FVB background
    • at a dose of 3U/kg 6-week old mice show a diminished response to insulin
    • circulating insulin levels in the fed state show that obese mice have exteme insulin resistance
  • endocrine/exocrine gland phenotype
  • abnormal islet of Langerhans morphology (J:78850)
    • some islets in obese mice have more than 1000 cells per cross section; such islets are absent in lean mice
    • increased pancreatic beta cell number (J:78850)
      • obese mice show massive expansion of beta cells (744 insulin +ve cells/islet cross-section in obese vs 165 +ve cells in lean mice); there are 4.5-fold more cells per islet cross-section in obese mice
  • digestive/alimentary phenotype
  • abnormal islet of Langerhans morphology (J:78850)
    • some islets in obese mice have more than 1000 cells per cross section; such islets are absent in lean mice
    • increased pancreatic beta cell number (J:78850)
      • obese mice show massive expansion of beta cells (744 insulin +ve cells/islet cross-section in obese vs 165 +ve cells in lean mice); there are 4.5-fold more cells per islet cross-section in obese mice
  • renal/urinary system phenotype
  • abnormal renal glomerulus morphology (J:78850)
    • at 7 months of age, obese mice show an increased mesangial matrix in most glomeruli compared to lean controls, resembling diabetic nephropathy; some small glomeruli have separated from the capsule with nearly obliterated microtubules

Leprdb/Leprdb

        B6.Cg-m +/+ Leprdb/J
  • growth/size phenotype
  • decreased body length (J:82334)
    • snout to anus length is decreased by about 5% compared to wild type mice
  • obese (J:103063)
    • develop progressive obesity
    • body weight is 2- to 3-fold more than in wild type mice by 10 weeks of age
    • body weight is 10% and 20% more in males and females, respectively, compared to Leprrtm1Mgmj homozygotes
    • increase in body weight becomes apparent at 4-6 weeks of age
  • behavior/neurological phenotype
  • polyphagia (J:82334)
  • cardiovascular system phenotype
  • abnormal myocardial fiber morphology (J:103063)
    • exhibit myocyte hypertrophy
  • left ventricle hypertrophy (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 (J:103063)
    • exhibit myocyte hypertrophy
  • homeostasis/metabolism phenotype
  • abnormal circulating lipid level (J:18161)
    • HDL cholesterol and glucose levels increase concurrently
    • plasma lipid levels are similiar at 3.5 and 14 months of age on the C57BL/6J background unlike on a C57BL/KsJ background
    • abnormal circulating cholesterol level (J:18161)
      • increased circulating cholesterol level (J:18161)
        • fasting plasma total cholesterol concentration is increased 2 fold over controls
        • increased circulating HDL cholesterol level (J:18161)
        • increased circulating LDL cholesterol level (J:18161)
        • increased circulating VLDL cholesterol level (J:18161)
    • increased circulating triglyceride level (J:82334)
      • triglyceride levels are elevated 1.5- to 2-fold
  • abnormal glucose homeostasis (J:82334)
    • increased circulating glucose level (J:82334)
    • increased circulating insulin level (J:82334)
  • abnormal interleukin level (J:115772)
    • elevated levels of IL-6 in bronchoalveolar lavage fluid
    • increased circulating interleukin-6 level (J:115772)
      • elevated levels of IL-6 in serum
  • decreased adiponectin level (J:115772)
    • decreased in serum
  • increased circulating leptin level (J:115772)
  • reproductive system phenotype
  • abnormal estrous cycle (J:82334)
    • females never show signs of vaginal oestrous
  • abnormal female reproductive anatomy (J:82334)
    • atrophy of the reproductive organs
  • abnormal ovulation (J:82334)
    • absent
  • female infertility (J:82334)
    • all females fail to reproduce
  • respiratory system phenotype
  • abnormal respiratory mechanics (J:115772)
    • end-expiratory pause increases considerably less than in controls after ozone exposure
    • abnormal functional residual capacity (J:115772)
      • reduced
      • pressure volume curves shifted to the right
    • abnormal lung compliance (J:115772)
      • total lung resistance increases much more in response to ozone than in control mice
      • responsiveness to methacholine and serotonin is much greater than controls
    • decreased pulmonary ventilation (J:115772)
      • ventilation volumes decline with ozone exposure but to a lesser degree than for controls
  • lung inflammation (J:115772)
    • elevated levels of eotaxin, Il6, keratinocyte cytokine, monocyte chemotactic protein-1, and neutrophiles in bronchoalveolar lavage as a result of ozone exposure
    • ozone induces significantly elevated levels of TNFR1
    • ozone induces a nonsignificant elevation of TNFR2 levels
    • elevated pulmonary levels of Il1beta mRNA 24 hours after ozone exposure
    • elevated pulmonary levels of TNF mRNA 24 hours after ozone exposure but to a lesser extent than in controls
  • immune system phenotype
  • abnormal inflammatory mediator physiology (J:115772)
    • abnormal chemokine level (J:115772)
      • elevated levels of eotaxin, keratinocyte cytokine, and monocyte chemotactic protein-1 (also elevated in serum) in bronchoalveolar lavage fluid
    • abnormal interleukin level (J:115772)
      • elevated levels of IL-6 in bronchoalveolar lavage fluid
      • increased circulating interleukin-6 level (J:115772)
        • elevated levels of IL-6 in serum
  • abnormal leukocyte morphology (J:115772)
    • decreased leukocyte cell number (J:115772)
      • decrease blood leukocyte numbers
    • increased neutrophil cell number (J:115772)
      • increased numbers in bronchoalveolar lavage
  • lung inflammation (J:115772)
    • elevated levels of eotaxin, Il6, keratinocyte cytokine, monocyte chemotactic protein-1, and neutrophiles in bronchoalveolar lavage as a result of ozone exposure
    • ozone induces significantly elevated levels of TNFR1
    • ozone induces a nonsignificant elevation of TNFR2 levels
    • elevated pulmonary levels of Il1beta mRNA 24 hours after ozone exposure
    • elevated pulmonary levels of TNF mRNA 24 hours after ozone exposure but to a lesser extent than in controls
  • tumorigenesis
  • increased metastatic potential (J:117826)
    • increased metastasis to the lung of both melanoma cell lines and lung cancer cell lines initially injected in the tail vein
  • hematopoietic system phenotype
  • abnormal leukocyte morphology (J:115772)
    • decreased leukocyte cell number (J:115772)
      • decrease blood leukocyte numbers
    • increased neutrophil cell number (J:115772)
      • increased numbers in bronchoalveolar lavage
  • endocrine/exocrine gland phenotype
  • abnormal hypothalamus physiology (J:6157)
  • nervous system phenotype
  • abnormal hypothalamus physiology (J:6157)

m/m

        DBA/J
  • pigmentation phenotype
  • diluted coat color (J:311)
    • coat color is not as diluted as that of homozygous dilute (Myo5ad) or homozygous leaden (Mlphln) mice
    • individual hairs have more cortical pigment than found in homozygous dilute or homozygous leaden mice
  • variable body spotting (J:311)
    • white tail tip with or without a white belly spot
  • skin/coat/nails phenotype
  • diluted coat color (J:311)
    • coat color is not as diluted as that of homozygous dilute (Myo5ad) or homozygous leaden (Mlphln) mice
    • individual hairs have more cortical pigment than found in homozygous dilute or homozygous leaden mice
  • variable body spotting (J:311)
    • white tail tip with or without a white belly spot

m/m

        B6.D2(Cg)-m
  • adipose tissue phenotype
  • abnormal brown adipose tissue amount (J:45425)
    • appeared to be completely absent in neonatal mice
  • decreased white adipose tissue amount (J:48831)
    • mice have 21% less inguinal adipose mass
  • growth/size phenotype
  • decreased body length (J:48831)
    • mutants are 8% shorter
  • decreased body weight (J:48831)
    • mutants weigh 15% less
  • hematopoietic system phenotype
  • platelet storage pool deficiency (J:45425)
    • platelet count, platelet serotonin and ATP levels normal
    • platelet ADP levels low
  • homeostasis/metabolism phenotype
  • increased bleeding time (J:45425)
  • platelet storage pool deficiency (J:45425)
    • platelet count, platelet serotonin and ATP levels normal
    • platelet ADP levels low

Gene & Allele Details

Allele Symbol Leprdb
Allele Name diabetes
Common Name(s) Lepdb; Lepr-; Leprdb-1J; db; leprdb;
Strain of OriginC57BLKS/J
Gene Symbol and Name Lepr, leptin receptor
Chromosome 4
Gene Common Name(s) CD295; Fa; LEPROT; Leprb; Modb1; OB-RGRP; OBR; db; diabetes; leptin receptor gene-related protein; obese-like; obl;
Molecular Note A G-to-T transversion in this allele created a donor splice site that causes abnormal splicing and a 106 nt insertion in the transcript, leading to premature termination of the long cellular domain of the Ob-Rb splice form and loss of its signal transducing function. [J:31324] [J:31327] [J:31488]
 
Allele Symbol m
Allele Name misty
Strain of OriginDBA/J

Control Information

  Control
   m +/+ Leprdb (Heterozygote from the colony)
   m +/m + from the colony
   000662 C57BLKS/J
 
  Considerations for Choosing Controls

Genotyping Protocols

Leprdb

Colony Maintenance

Breeding & HusbandrySince both males and females homozygous for Leprdb are sterile, the closely linked coat color mutation, m, has been incorporated into stocks for maintenance of the db mutation. Breeding is performed by mating repulsion double heterozygotes, m +/+ Leprdb, which presumably yield 1/4 diabetics (black, obese at weaning) for studies , 1/2 wild type repulsion double heterozygotes (black, lean) for futher breeding, and 1/4 misty mice (grey, lean) that can be discarded. The risk of recombination between the m and Leprdb loci is only about 2%, recognizable in pups as young as 3 days old by absence of pigment in paws and tip of tail. Dietary restrictions can prolong life and carbohydrate-free, protein-enriched defined diets can diminish the significantly the severity of the disease.
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying   Leprdb     (8 strains)

View Strains carrying   m     (9 strains)

Strains carrying other alleles of Lepr
000709   129P3/J-Leprdb-3J/J
004939   NOD/ShiLtJ-Leprdb-5J/LtJ
006846   STOCK Leprdb-9J/Jgn
View Strains carrying other alleles of Lepr     (3 strains)

Phenotypic Data

Body Weight Information - JAX® Mice Strain BKS.Cg-m +/+ Leprdb/J (000642)
(This chart reflects the typical correlation between body weight and age for mice maintained in production colonies at The Jackson Laboratory.)
Mouse Phenome Database

Additional Web Information

Congenic Nomenclature
Diet Change Notification
Genetic Quality Control Annual Report
JAX Notes, Spring 2003; 489. Malocclusion in the Laboratory Mouse.
JAX Notes, Summer 2003; 490. Hydrocephalus in Laboratory Mice.
JAX Notes, Summer 2008; 510. BKS.Cg-m +/+ Leprdb/J (000642), One of the Most Widely-used Diabetes Models at JAX

Animal Health Reports

Room Number           AX5 - Pairs shipped from this room
Room Number           AX8

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)

Leprdb 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, morbid, with hypogonadism (rare)

Reproductive Biology Research
Fertility Defects

m related

Dermatology Research
Color and White Spotting Defects

References

Selected Reference(s)

Chen H; Charlat O; Tartaglia LA; Woolf EA; Weng X; Ellis SJ; Lakey ND; Culpepper J; Moore KJ; Breitbart RE; Duyk GM; Tepper RI; Morgenstern JP. 1996. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84(3):491-5. [PubMed: 8608603]  [J:31324]

Chua SC Jr; Chung WK; Wu-Peng XS; Zhang Y; Liu SM; Tartaglia L; Leibel RL. 1996. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor [see comments] Science 271(5251):994-6. [PubMed: 8584938]  [J:31419]

Dardenne M; Savino W; Bach JF. 1984. Autoimmune mice develop antibodies to thymic hormone: production of anti-thymulin monoclonal autoantibodies from diabetic (db/db) and B/W mice. J Immunol 133(2):740-3. [PubMed: 6539799]  [J:109953]

Fantuzzi G; Faggioni R. 2000. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68(4):437-46. [PubMed: 11037963]  [J:109886]

Gueorguiev M; Goth ML; Korbonits M. 2001. Leptin and puberty: a review. Pituitary 4(1-2):79-86. [PubMed: 11824512]  [J:109856]

Hummel KP; Dickie MM; Coleman DL. 1966. Diabetes, a new mutation in the mouse. Science 153(740):1127-8. [PubMed: 5918576]  [J:5010]

Kampfer H; Paulukat J; Muhl H; Wetzler C; Pfeilschifter J; Frank S. 2000. Lack of interferon-gamma production despite the presence of interleukin-18 during cutaneous wound healing. Mol Med 6(12):1016-27. [PubMed: 11474118]  [J:109870]

Lee GH; Proenca R; Montez JM; Carroll KM; Darvishzadeh JG; Lee JI; Friedman JM. 1996. Abnormal splicing of the leptin receptor in diabetic mice. Nature 379(6566):632-5. [PubMed: 8628397]  [J:31327]

Leiter EH; Chapman HD. 1994. Obesity-induced diabetes (diabesity) in C57BL/KsJ mice produces aberrant trans-regulation of sex steroid sulfotransferase genes. J Clin Invest 93(5):2007-13. [PubMed: 8182132]  [J:17991]

Mandel MA; Mahmoud AA. 1978. Impairment of cell-mediated immunity in mutation diabetic mice (db/db). J Immunol 120(4):1375-7. [PubMed: 347001]  [J:109964]

Serreze DV; Leiter EH; Kuff EL; Jardieu P; Ishizaka K. 1988. Molecular mimicry between insulin and retroviral antigen p73. Development of cross-reactive autoantibodies in sera of NOD and C57BL/KsJ db/db mice. Diabetes 37(3):351-8. [PubMed: 3286334]  [J:27625]

Yoon JW; Leiter EH; Coleman DL; Kim MK; Pak CY; McArthur RG; Roncari DA. 1988. Genetic control of organ-reactive autoantibody production in mice by obesity (ob) diabetes (db) genes. Diabetes 37(9):1287-93. [PubMed: 3044893]  [J:109940]

Additional References

Price and Supply Information

Strain Name: BKS.Cg-m +/+ Leprdb/J
Stock Number: 000642

Price Details

IMPORTANT NOTE: Prices are based on shipping destination. To view prices, select your shipping destination.

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Supply Details

Standard SupplyLevel 2. Up to 100 mice. Larger quantities or custom orders arranged upon request.
Supply Notes Mice are not available until four weeks of age.
Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available.
Strains that must be genotyped are not available until five to seven weeks of age.
This strain is available from some international Charles River Laboratories (CRL) breeding facilities in Japan and/or Europe. For more information, see the Worldwide Distributor List for JAX® Mice.
Genomic DNA is available for this strain from the Mouse DNA Resource.
LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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