Overview

Also Known As:B6-diabetes

These mice carry a spontaneous mutation at the Lepr locus on a C57BL/6J background and are characterized by compensatory hyperplasia of the islet B-cells and hyperinsulinemia. Wound healing is delayed, and metabolic efficiency is increased. The strain carries the misty mutation (Dock7^m) to aid in early identification of homozygotes.

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Dock7^m

Allele Type	Gene Symbol	Gene Name
Spontaneous	Dock7	dedicator of cytokinesis 7

Lepr^db

Allele Type	Gene Symbol	Gene Name
Spontaneous	Lepr	leptin receptor

View Genetics

Research Applications

Mouse/Human Gene Homologs
Diabetes and Obesity Research
Endocrine Deficiency Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Reproductive Biology Research
Dermatology Research
Metabolism Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Mice homozygous for the diabetes spontaneous mutation (Lepr^db) become identifiably obese around 3 to 4 weeks of age. Elevations of plasma insulin begin at 10 to 14 days and of blood sugar at 4 to 8 weeks. Affected mice are polyphagic, polydipsic, and polyuric. The course of the disease is markedly influenced by genetic background. On the C57BL/6 background there is compensatory hyperplasia of the islet B-cells, and continued hyperinsulinemia throughout an 18- to 20-month life span. Wound healing is delayed, and metabolic efficiency is increased. Although normal in body weight, blood glucose, and plasma insulin, heterozygotes (Lepr^db/+) 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 Lepr^db may cause a defect in the hypothalamus. Steroid sulfotransferase enzymes, aberrantly expressed in diabetic mice, interact with the Lepr^db mutation as modifiers of gender differences in obesity-induced diabetes susceptibility. Because Lepr^db homozygotes are functionally sterile, the coat color marker misty (Dock7^m) has been incorporated into stocks for maintenance of the diabetes mutation. The coupling double heterozygote, (Dock7^m Lepr^db/+ +, this strain) allows identification of homozygotes before the phenotype becomes severe.

The recessive misty mutation causes a mild dilution of coat color. On certain backgrounds, a white tail tip often accompanied by a belly spot is also present. Melanocytes from homozygous misty mice (Dock7^m/Dock7^m) have a highly dendritic shape, show deficient proliferation in culture and have much more melanin content. Fewer melanoblasts are found in primary cultures from Dock7^m/Dock7^m mice than from wildtype controls. Between two and five weeks of age, Dock7^m/Dock7^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, bleed time is increased and platelet AD levels are reduced in Dock7^m/Dock7^m homozygotes. (Woolley, 1941 and 1945; Truett et al. 1998; Sviderskaya et al. 1998.)

Development

The strain was cryopreserved in 1990 at generation N6F36.

Control Suggestions

Untyped from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Dock7^m

Allele Symbol: Dock7^m

Allele Name	misty
Allele Type	Spontaneous
Allele Synonym(s)	m
Gene Symbol and Name	Dock7, dedicator of cytokinesis 7
Gene Synonym(s)
Strain of Origin	DBA/J
Chromosome	4
Molecular Note	Crosses between mice homozygous for misty and for moonlight, which mapped to overlapping critical regions on Chr 4, demonstrated failure of the two mutations to complement one another. Once moonlight had been identified as a mutation of Dock7 (Dock7^mnlt), sequence analysis of this gene from misty mice revealed a retrotransposon LTR insertion following nucleotide 2045 (numbering from the A of the transcription initiation codon) that interrupts exon 18 and shifts the reading frame after codon 682 so that ten incorrect amino acids are incorporated into the protein before its premature termination.

Lepr^db

Allele Symbol: Lepr^db

Allele Name	diabetes
Allele Type	Spontaneous
Allele Synonym(s)	db; db/db; Lep^db; Lepr-; Lepr^db-1J; leprdb
Gene Symbol and Name	Lepr, leptin receptor
Gene Synonym(s)
Strain of Origin	C57BLKS/J
Chromosome	4
General Note	Phenotypic Similarity to Human Syndrome: Gestational Diabetes J:219658
Molecular Note	An intronic G-to-T transversion in this allele created a donor splice site that causes abnormal splicing and the inclusion of 106 nt of intronic sequence 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.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

non-alcoholic fatty liver disease

Research Areas By Phenotype

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

Genotype: Lepr^db related

Mouse/Human Gene Homologs
- obesity, morbid, with hypogonadism (rare)
Diabetes and Obesity Research
- Obesity With Diabetes
- Impaired Wound Healing
- Hyperinsulinemia
- Insulin Resistance
Endocrine Deficiency Research
- Adipose Defects
- Hypothalamus/Pituitary Defects
- Pancreas Defects
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency Associated with Other Defects
Internal/Organ Research
- Adipose Defects
Reproductive Biology Research
- Fertility Defects
Metabolism Research

Diabetes and Obesity Research
- Hyperglycemia
  - transient
- Type 2 Diabetes (NIDDM)
  - transient

Genotype: Dock7^m related

Dermatology Research
- Color and White Spotting Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Lepr^db/Lepr^db
involves: C57BLKS/J

adipose tissue phenotype

abnormal adipose tissue morphology
- increase in adipose tissue weight in both males and females

abnormal white adipose tissue morphology
- subcutaneous white adipose tissue (sWAT) has less uridine content than in wild-type mice

increased total body fat amount
- increase in total fat content

cardiovascular system phenotype

abnormal blood circulation
- reduced aortic flow

abnormal cardiovascular system physiology
- at low fatty acid supply, hearts consume 86% more oxygen (MV_O2) for noncontractile purposes compared with control hearts and a further increase in fatty acid supply has no effect on the already elevated unloaded MV_O2, indicating reduced cardiac efficiency in unloaded hearts

abnormal myocardium layer morphology
- myocardial triacylglycerol content 2X that of controls at 10-18 weeks of age

abnormal vascular wound healing
- reduced neointimal area relative to controls 4 weeks after femoral artery injury
- vascular smooth muscle proliferation significantly reduced

altered response to myocardial infarction
- 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

cardiac ischemia
- reduced recovery of mechanical function after 13 minutes of ischemia and reperfusion

decreased cardiac muscle contractility
- hearts show a significant increase in the slope of the MV_O2-PVA (pressure volume area) regression line after elevation of fatty acids, suggesting a reduction in contractile efficiency

decreased cardiac output
- cardiac output is reduced in fatty acid perfused hearts

decreased heart rate
- intrinsic heart rates are reduced at all workloads

decreased systemic arterial blood pressure

decreased systemic arterial systolic blood pressure
- decreased peak systolic pressure
- decreased peak systolic pressure X cardiac output
- decreased peak systolic pressure X heart rate

increased left ventricle diastolic pressure
- hearts show a significant increase in the slope of the MV_O2-PVA (pressure volume area) regression line after elevation of fatty acids, suggesting a reduction in contractile efficiency

increased vasoconstriction
- hypercontractility corrollated with the levels of obesity, hyperglycemia, and hyperinsulinemia
- hypercontractility of smooth muscle in aortic strips due to either phenylephrine or serotonin
- maximal contractions increase with age rather than decrease as in controls

nervous system phenotype

abnormal hypothalamus physiology
- hypothalamic uptake of norepinephrine is decreased in males

renal/urinary system phenotype

abnormal kidney calyx morphology
- calyceal dilation eventually develops

abnormal kidney papilla morphology
- eventually becomes flattened

abnormal renal glomerulus morphology
- basement membrane becomes thickened with age

increased kidney weight

increased urine protein level
- 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

polyuria

renal glomerular immunoglobulin deposits

renal glomerular protein deposits
- large quantites of immunoglobulin and complement are found in the mesangium

reproductive system phenotype

abnormal endometrium morphology
- basal membrane of epithelial cells displays a folded contour at locations where lipid accumulates
- increased volume and density of lipid inclusion vacuoles
- tissue norepinephrin levels elevated by 4 weeks of age and remain elevated

abnormal uterus morphology

decreased uterus weight
- 1/3 normal tissue weight by 12 weeks
- decreased relative to controls by 4 weeks of age

vision/eye phenotype

abnormal intraocular pressure
- modest but significant elevation of intraocular pressure

cellular phenotype

abnormal aerobic respiration
- carbohydrate oxidation becomes reduced
- elevation of fatty acids in perfused hearts causes an increase in fatty acid oxidation combined with a reduction in glucose oxidation rates
- palmitate oxidation is elevated

abnormal respiratory electron transport chain
- state 3 respiration is elevated in cardiac mitochondria incubated with palmitoyl-carnitine but not with pyruvate

endocrine/exocrine gland phenotype

abnormal pancreatic beta cell morphology
- individual beta cell size is increased

abnormal pancreatic beta cell physiology
- beta cells exhibit DNA damage unlike control cells

abnormal pancreatic islet morphology
- islet mass and density are significantly increased compared to wild-type mice

growth/size/body region phenotype

decreased body length
- mutants are about 5% shorter than controls

increased body weight
- by four weeks of age
- overweight by 4 weeks of age

increased kidney weight

increased liver weight

obese

behavior/neurological phenotype

abnormal conditioned taste aversion behavior
- 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

polyphagia

hematopoietic system phenotype

increased glycosylated hemoglobin level
- significant increase in the percentage of plasma glycosylated hemoglobin

homeostasis/metabolism phenotype

abnormal glucose homeostasis
- diabetic phenotype appears earlier in males than in females

abnormal nucleotide metabolism
- however, epididymal white adipose tissue (eWAT), interscapular brown adipose tissue (BAT), and liver uridine content are not different
- subcutaneous white adipose tissue (sWAT) has less uridine content than in wild-type mice

abnormal vascular wound healing
- reduced neointimal area relative to controls 4 weeks after femoral artery injury
- vascular smooth muscle proliferation significantly reduced

altered response to myocardial infarction
- 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

decreased circulating glucose level
- 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
- mice treated with an adenovirus expressing Adipor 2 show improved glucose resistance and decreased plasma insulin level

hyperglycemia
- at 12 weeks
- by 8 weeks
- diabetes is improved after treatment with an adenovirus expressing Adipor1 or Adipor2

hyperlipidemia

impaired adaptive thermogenesis
- 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
- sympathetic activity

impaired glucose tolerance

increased circulating cholesterol level

increased circulating corticosterone level

increased circulating free fatty acid level

increased circulating glucose level
- plasma fasting glucose is increased

increased circulating insulin level
- fasting insulin is increased
- hyperinsulinemia by 8 weeks

increased circulating leptin level

increased circulating triglyceride level

increased glycosylated hemoglobin level
- significant increase in the percentage of plasma glycosylated hemoglobin

increased urine protein level
- 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

insulin resistance
- mice treated with an adenovirus expressing Adipor1 or Adipor 2 show improved insulin resistance

immune system phenotype

increased susceptibility to autoimmune diabetes
- T cells from homozygous mice but not those from heterozygous mice suppressed the beta cell response to glucose + theophylline

liver/biliary system phenotype

increased liver weight

mortality/aging

increased sensitivity to induced morbidity/mortality
- 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
- 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

muscle phenotype

abnormal myocardium layer morphology
- myocardial triacylglycerol content 2X that of controls at 10-18 weeks of age

decreased cardiac muscle contractility
- hearts show a significant increase in the slope of the MV_O2-PVA (pressure volume area) regression line after elevation of fatty acids, suggesting a reduction in contractile efficiency

increased vasoconstriction
- hypercontractility corrollated with the levels of obesity, hyperglycemia, and hyperinsulinemia
- hypercontractility of smooth muscle in aortic strips due to either phenylephrine or serotonin
- maximal contractions increase with age rather than decrease as in controls

Genotype: Lepr^db/Lepr^db
C57BLKS/J-Lepr

behavior/neurological phenotype

polyphagia

homeostasis/metabolism phenotype

decreased body temperature

hyperglycemia

hyperlipidemia

increased circulating cholesterol level

increased circulating free fatty acid level

increased circulating insulin level

increased circulating leptin level

increased circulating triglyceride level

cardiovascular system phenotype

abnormal cardiovascular system physiology

decreased cardiac output

decreased heart rate

liver/biliary system phenotype

increased liver weight

renal/urinary system phenotype

increased kidney weight

growth/size/body region phenotype

increased kidney weight

increased liver weight

obese

Genotype: Lepr^db/Lepr^db
FVB.BKS-Lepr

endocrine/exocrine gland phenotype

increased pancreatic beta cell number
- 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

pancreatic islet hyperplasia
- some islets in obese mice have more than 1000 cells per cross section; such islets are absent in lean mice

renal/urinary system phenotype

abnormal renal glomerulus morphology
- 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

growth/size/body region phenotype

obese
- mice of both sexes are obese

homeostasis/metabolism phenotype

abnormal circulating glucose level
- Background Sensitivity - after a 2-day fast on refeeding with carbohydrate-free diet, female obese mice show a rise in glucose

hyperglycemia
- fasting mice are hyperglycemic at 3 months of age, while obese B6.BKS-Lepr^db 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-Lepr^db females (~50 ng/ml)
- Background Sensitivity - obese mice have a prolonged period of hyperglycemia compared to obese B6.BKS-Lepr^db mice where glucose levels rarely exceed 250 mg/dl

impaired glucose tolerance
- Background Sensitivity - 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-Lepr^db mice clear glucose load by 90 min
- Background Sensitivity - obese mice show a rapid increase of blood glucose above 400 mg/dl with diminished rate of glucose clearance

increased circulating insulin level
- Background Sensitivity - /ml)
- Background Sensitivity - at 3 months of age, females show a trend toward higher insulin levels compared to obese B6.BKS-Lepr^db females; at 5-7 months insulin levels (~500 ng/ml) are ~10-fold higher than levels in obese female obese B6.BKS-Lepr^db mice (~50 ng/ml)

insulin resistance
- 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

Genotype: Lepr^db/Lepr^db
BKS.Cg-Dock7 +/+ Lepr/J

behavior/neurological phenotype

abnormal food intake
- food intake is about 60% of control level

abnormal learning/memory/conditioning

abnormal locomotor circadian rhythm
- daily locomotor activity rhythmicity severely diminished at 13-14 weeks, 75% fail to show significant rhythmicity
- daily locomotor pattern becomes attenuated in 6-8 week old mice but rhythmicity is retained
- daily locomotor rhythmicity restored by feeding restriction during dark phase

abnormal spatial learning
- longer swimming distances than control mice in a Morris water maze test

abnormal spatial reference memory
- cross the original platform location less frequently than do controls in a Morris water maze test

cellular phenotype

abnormal axon extension
- axonal growth cone extension fails to occur for neurons treated in culture with 100ng/ml of leptin

endocrine/exocrine gland phenotype

increased glucagon secretion
- increased secreation of glucagon by pancreatic cells in culture

growth/size/body region phenotype

increased body weight

obese
- become progressively obese starting at 5 weeks of age
- weight reaches 2.5X that of control mice by 3 months of age

weight loss
- body weight drops after 6 days on feeding restriction during the dark phase

homeostasis/metabolism phenotype

abnormal circulating cholesterol level

abnormal circulating glucose level

abnormal circulating lipid level
- Background Sensitivity - but have significantly higher plasma triglyceride levels
- Background Sensitivity - 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

albuminuria
- moderate albuminuria is observed at 26 weeks of age

decreased circulating glucose level
- affect of BDNF on blood glucose becomes progressively less as mice age
- brain derived neurotrophic factor (BDNF) causes a drop in blood glucose relative to controls 8 weeks after treatment
- glucose levels are reduced at all times tested when mice are placed on feeding restriction during the dark phase
- neurotrophin 3 also causes a drop in blood glucose but the glucose levels return to normal by 24 hours after treatment

decreased circulating insulin level
- BDNF causes a 50% reduction in plasma insulin relative to controls
- morning insulin levels lowered when feeding is restricted during the dark phase

decreased circulating triglyceride level
- triglyceride levels are reduced at all times tested when mice are placed on feeding restriction during the dark phase

decreased prostaglandin level
- in diabetic wounds, PGE2 level is consistently less than 50% of wild-type wounds at all times

decreased urine albumin level
- )
- 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)

delayed wound healing
- T26A, a prostaglandin transporter inhibitor, topically applied to wounds shortened wound closure to 16 days in mutants, similar to untreated controls; T26A increased re-epithelialization, neovascularization, and blood flow in wounds
- wound healing is impaired, with an average wound closure time of 22 days, 7 days longer than in controls

hyperglycemia
- fasting blood glucose level is significantly higher than control at 26 weeks of age

improved glucose tolerance
- BDNF treatment causes a lower blood glucose level response in a glucose tolerance test

increased circulating cholesterol level
- fasting plasma total cholesterol concentration is increased 2 fold over controls

increased circulating glucose level
- blood glucose shows a progressive increase from 5 through 33 weeks

increased circulating HDL cholesterol level

increased circulating LDL cholesterol level

increased circulating triglyceride level
- triglyceride levels are elevated 1.5- to 2-fold

increased circulating VLDL cholesterol level

increased glucagon secretion
- increased secreation of glucagon by pancreatic cells in culture

muscle phenotype

abnormal myocardial fiber morphology
- dense bodies present in places normally occupied by mitochondria
- disrupted sarcomeres sometimes
- presence of many lipid droplets

nervous system phenotype

abnormal axon extension
- axonal growth cone extension fails to occur for neurons treated in culture with 100ng/ml of leptin

abnormal axon morphology
- non significant shift toward smaller fiber diameter at 15 weeks of age
- shift of unmyelinated fibers to smaller diameters
- significantly shifted to smaller diameter fibers by 25 weeks in ventral roots, dorsal roots, sural nerve
- small numbers of very large unmyelinated fibers (up to 1.6 micrometers)
- smaller diameter nerve fibers in peroneal, phrenic and vagus nerves at 25 weeks but not significant

abnormal CNS synaptic transmission

abnormal myelin sheath morphology
- number of myelin lamellae relative to nerve diameter is increased

abnormal nerve conduction
- insulin treatment results in improved conductance but only for the duration of treatment and control levels of conductance are never restored
- motor nerve conductance significantly lower than controls from 7 weeks of age onward
- no conductance improvement is seen in mice over 23 weeks in age due to insulin treatment
- velocity returns to and is maintained at prediabetic levels by 15 weeks of age whereas control mice show a continuous increase in velocity

abnormal nervous system morphology

absent long term depression
- CA1 hippocampal slices indicate no long term depression on recordings of excitatory post-synaptic potentials

decreased motor neuron number
- myelinated fiber density increases in most nerves (not the peroneal and phrenic nerves)
- myelinated fibers reduced in numbers at 25 weeks in the sural nerve
- unmyelinated fiber density increase in the sural, peroneal, and vagus nerves
- unmyelinated fibers reduced in numbers at 25 weeks in the vagus nerve

reduced long term potentiation
- CA1 hippocampal slices indicate brief post tetanic potentiation but no long term potentiation on recordings of excitatory post-synaptic potentials

renal/urinary system phenotype

albuminuria
- moderate albuminuria is observed at 26 weeks of age

decreased urine albumin level
- )
- 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)

expanded mesangial matrix
- moderate mesangial expansion is observed in glomeruli at 26 weeks

increased creatinine clearance
- ght)
- 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)

vision/eye phenotype

abnormal eye electrophysiology
- delays in oscillatory potentials 1, 2, 3 although only the delay in "OP1" is significant
- prolonged latency of the b-wave in the retina

cardiovascular system phenotype

abnormal myocardial fiber morphology
- dense bodies present in places normally occupied by mitochondria
- disrupted sarcomeres sometimes
- presence of many lipid droplets

abnormal vascular development
- dense bodies found in the smooth muscle of intramyocardial arteries

Genotype: Lepr^db/Lepr⁺
B6.Cg-Dock7 +/+ Lepr/J

growth/size/body region phenotype

increased body weight
- slight but significant increase in body weight compared to wild-type mice

mortality/aging

extended life span
- increased survival when totally deprived of food than wild-type controls
- Background Sensitivity - survival when deprived of food is not as long as when in a C57BLKsS background

Genotype: Lepr^db/Lepr^db
BKS.Cg-Dock7 +/+ Lepr/OlaHsd

digestive/alimentary phenotype

abnormal digestive system physiology
- transepithelial resistance in the epithelium is reduced, indictive of a disrupted mucosal barrier function

abnormal intestinal epithelium morphology
- reduced levels of occludin in intestinal sections
- zonula occludens 1 has a discontinuous distribution

immune system phenotype

abnormal acute inflammation
- higher levels of endotoxin are found in portal blood (entotoxemia)

abnormal chemokine secretion
- increased release of monocyte chemo attractant protein by hepatic stellate cells

increased interleukin-6 secretion
- increased release by hepatic stellate cells

increased susceptibility to endotoxin shock
- increased succeptibility of hepatic stellate cells to LPS

liver inflammation

liver/biliary system phenotype

liver inflammation

Genotype: Lepr^db/Lepr⁺
involves: C57BLKS/J

adipose tissue phenotype

increased total body fat amount
- 20% greater adipose tissue mass during pregnancy than in controls

homeostasis/metabolism phenotype

abnormal circulating insulin level
- 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

abnormal glucose homeostasis

abnormal hormone level
- elevated placental leptin levels in pregnant females

decreased circulating insulin level
- pregnant dams exhibit lower fasting insulin levels than wild-type mothers

impaired glucose tolerance
- 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
- both male and female heterozygous offspring have impaired glucose tolerance irrespective of maternal environment (heterozygous or wild-type mothers)
- females exhibit impaired glucose tolerance during pregnancy
- glucose levels 41% higher in a glucose tolerance test at 30 and at 60 minute time points
- profound glucose intolerance during pregnancy

increased circulating glucose level
- fasting glucose levels elevated 25% during pregnancy

increased circulating leptin level
- heterozygous offspring exhibit an increase in leptin levels at 6 months of age
- mothers exhibit higher circulating leptin levels than wild-type mothers

behavior/neurological phenotype

increased food intake
- food intake 11% greater than controls during pregnancy
- leptin treatment suppresses food intake to near control levels

cellular phenotype

maternal effect
- offspring born from heterozygous mothers with gestational diabetes have lower fasting insulin levels and worse glucose tolerance than offspring born from wild-type mothers
- wild-type males born to heterozygous mothers are heavier than wild-type mice born to wild-type mothers, but postnatal weight gain of female offspring is not affected by the maternal environment

embryo phenotype

enlarged placenta
- placentas from heterozygous fetuses are larger than those of wild-type fetuses, irrespective of maternal genotype

growth/size/body region phenotype

increased birth weight
- heterozygous fetuses carried by wild-type dams exhibit a 5% higher birth weight than wild-type littermates
- heterozygous fetuses from heterozygous mothers are 3% bigger than wild-type littermates
- Normal - however, wild-type pups from heterozygous mothers are no bigger than wild-type fetuses carried by wild-type mothers

increased body weight
- heterozygous pregnant dams are heavier than wild-type mothers at E18.5
- male and female heterozygous offspring from both normal and complicated pregnancies, are heavier than wild-type littermates at 3 and 6 months of age

increased susceptibility to weight gain
- 33% greater maternal weight gain
- birth weights significantly heavier than controls and unaffected by maternal leptin treatment unlike controls where maternal leptin treatment causes a decrease in birth weights
- maternal body weight at term 24% greater than controls

Genotype: Dock7^m/Dock7⁺ Lepr^db/Lepr⁺
BKS.Cg-Dock7 +/+ Lepr/J

mortality/aging

extended life span
- increased survival when totally deprived of food than wild-type controls
- Background Sensitivity - survival when deprived of food is longer rhan when in a C57BL/6 background

Genotype: Lepr^db/Lepr^db
involves: 129S2/SvPas * C57BL/6 * C57BLKS/J

renal/urinary system phenotype

abnormal kidney morphology
- total kidney collagen is increased in females by 96%

abnormal renal glomerulus morphology
- any genotype
- glomerular extracellular matrix (ECM) area in females is increased by 31% compared to wild-type female controls and female single Serpine1-deficient animals; however, when expressed as fractional glomerular ECM area, little difference is observed between any genotype

Genotype: Lepr^db/Lepr^db
BKS.Cg-Dock7 +/+ Lepr/Jcl

adipose tissue phenotype

abnormal epididymal fat pad morphology
- the epididymal fat pad exhibits macrophage infiltration unlike in wild-type mice

cellular phenotype

increased pancreatic islet cell apoptosis
- pancreatic islet cell apoptosis is increased compared to in heterozygous mice

endocrine/exocrine gland phenotype

abnormal pancreas physiology
- at 8 weeks, pancreatic islet cell proliferation is increased compared to in heterozygous mice
- Normal - however, pancreatic islet cell proliferation by 16 weeks is normal

increased pancreatic beta cell mass

increased pancreatic islet cell apoptosis
- pancreatic islet cell apoptosis is increased compared to in heterozygous mice

homeostasis/metabolism phenotype

hyperglycemia

increased circulating insulin level

Genotype: Lepr^db/Lepr^db
B6.BKS(D)-Lepr/J

behavior/neurological phenotype

abnormal behavior
- faster in food finding trials relative to controls

hypoactivity
- during the dark phase

homeostasis/metabolism phenotype

abnormal response/metabolism to endogenous compounds
- mice treated with leptin fail to exhibit a decrease in food intake unlike similarly treated wild-type mice

decreased body temperature

decreased carbon dioxide production

decreased oxygen consumption

impaired glucose tolerance

insulin resistance

renal/urinary system phenotype

glomerulosclerosis
- homozygotes develop significant glomerulosclerosis by 18 weeks of age

The following phenotype relates to a compound genotype created using this strain

Genotype: Lepr^db/Lepr^db
B6.Cg-Dock7 +/+ Lepr/J

behavior/neurological phenotype

polyphagia

reduced male mating frequency

hematopoietic system phenotype

abnormal leukocyte morphology

decreased leukocyte cell number
- decrease blood leukocyte numbers

increased neutrophil cell number
- increased numbers in bronchoalveolar lavage

homeostasis/metabolism phenotype

abnormal chemokine level
- elevated levels of eotaxin, keratinocyte cytokine, and monocyte chemotactic protein-1 (also elevated in serum) in bronchoalveolar lavage fluid

abnormal circulating cholesterol level

abnormal circulating lipid level
- HDL cholesterol and glucose levels increase concurrently
- Background Sensitivity - plasma lipid levels are similar at 3.5 and 14 months of age on the C57BL/6J background unlike on a C57BL/KsJ background

abnormal glucose homeostasis

abnormal hormone level
- female mice exhibit an increase in hypothalamic gonadotrophin releasing hormone compared to in wild-type mice

abnormal interleukin level
- elevated levels of IL-6 in bronchoalveolar lavage fluid

decreased circulating adiponectin level
- decreased adiponectin levels in serum

hyperglycemia

increased circulating cholesterol level
- fasting plasma total cholesterol concentration is increased 2 fold over controls

increased circulating glucose level

increased circulating HDL cholesterol level

increased circulating insulin level

increased circulating interleukin-6 level
- elevated levels of IL-6 in serum

increased circulating LDL cholesterol level

increased circulating leptin level

increased circulating triglyceride level
- triglyceride levels are elevated 1.5- to 2-fold

increased circulating VLDL cholesterol level

cardiovascular system phenotype

abnormal myocardial fiber morphology
- exhibit myocyte hypertrophy

heart left ventricle hypertrophy
- 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

immune system phenotype

abnormal chemokine level
- elevated levels of eotaxin, keratinocyte cytokine, and monocyte chemotactic protein-1 (also elevated in serum) in bronchoalveolar lavage fluid

abnormal interleukin level
- elevated levels of IL-6 in bronchoalveolar lavage fluid

abnormal leukocyte morphology

decreased leukocyte cell number
- decrease blood leukocyte numbers

increased circulating interleukin-6 level
- elevated levels of IL-6 in serum

increased neutrophil cell number
- increased numbers in bronchoalveolar lavage

lung inflammation
- elevated levels of eotaxin, Il6, keratinocyte cytokine, monocyte chemotactic protein-1, and neutrophiles in bronchoalveolar lavage as a result of ozone exposure
- 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
- ozone induces a nonsignificant elevation of TNFR2 levels
- ozone induces significantly elevated levels of TNFR1

muscle phenotype

abnormal myocardial fiber morphology
- exhibit myocyte hypertrophy

heart left ventricle hypertrophy
- 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

neoplasm

increased metastatic potential
- increased metastasis to the lung of both melanoma cell lines and lung cancer cell lines initially injected in the tail vein

nervous system phenotype

abnormal hypothalamus physiology

reproductive system phenotype

abnormal female reproductive system morphology
- atrophy of the reproductive organs

absent estrous cycle
- mice exhibit diestrous vaginal acyclicity or occasional metestrous acyclicity

absent estrus
- females never show signs of vaginal oestrous

anovulation

constricted vagina orifice

female infertility
- all females fail to reproduce

small uterus

growth/size/body region phenotype

decreased body length
- snout to anus length is decreased by about 5% compared to wild-type mice

heart left ventricle hypertrophy
- 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

obese
- body weight is 10% and 20% more in males and females, respectively, compared to Leprr^tm1Mgmj homozygotes
- body weight is 2- to 3-fold more than in wild-type mice by 10 weeks of age
- develop progressive obesity
- increase in body weight becomes apparent at 4-6 weeks of age

respiratory system phenotype

abnormal functional residual capacity
- pressure volume curves shifted to the right
- reduced

abnormal lung compliance
- responsiveness to methacholine and serotonin is much greater than controls
- total lung resistance increases much more in response to ozone than in control mice

abnormal respiratory mechanics
- end-expiratory pause increases considerably less than in controls after ozone exposure

decreased pulmonary ventilation
- ventilation volumes decline with ozone exposure but to a lesser degree than for controls

lung inflammation
- elevated levels of eotaxin, Il6, keratinocyte cytokine, monocyte chemotactic protein-1, and neutrophiles in bronchoalveolar lavage as a result of ozone exposure
- 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
- ozone induces a nonsignificant elevation of TNFR2 levels
- ozone induces significantly elevated levels of TNFR1

Genotype: Lepr^db/Lepr^db
B6.BKS(D)-Lepr/JOrlRj

cellular phenotype

increased hepatocyte apoptosis
- some hepatocyte apoptosis is seen in mice fed the standard diet and apoptosis is not increased by a high-calorie diet and even reduced after 3 months of a high-calorie diet

growth/size/body region phenotype

increased body weight
- mice exhibit increased body weight at 3 months, but not 1 month, of standard chow diet

increased susceptibility to diet-induced obesity
- mice exhibit increased body weight when fed a high-calorie diet for 1 or 3 months

homeostasis/metabolism phenotype

increased cholesterol level
- total cholesterol levels are increased in mice fed a high-calorie diet for 1 month and increased further when fed for 3 months

increased circulating ketone body level
- plasma beta-hydroxybutyrate levels are greatly increased after 3 months of the high-calorie diet

increased susceptibility to diet-induced obesity
- mice exhibit increased body weight when fed a high-calorie diet for 1 or 3 months

immune system phenotype

liver inflammation
- hepatic necroinflammation is not prominent, however it is aggravated after 1 month of high-calorie diet compared to standard diet and tends to alleviate with time
- non-alcoholic steatohepatitis is seen occasionally after 3 months of a standard diet and is seen in 3 of 9 mice after 3 months of the high-calorie diet

liver/biliary system phenotype

hepatic steatosis
- macrovacuolar steatosis is similar to that seen in Lep^ob> homozygotes
- mice develop steatosis, with steatosis mainly localized in the centrilobular and mediolobular areas; fatty change is milder than in Lep^ob homozygotes
- microvesicular steatosis is more frequently seen than in Lep^ob homozygotes
- severity of steatosis is enhanced by the high-calorie diet after 1 month, but is subsequently reduced after 3 months on this diet

increased hepatocyte apoptosis
- some hepatocyte apoptosis is seen in mice fed the standard diet and apoptosis is not increased by a high-calorie diet and even reduced after 3 months of a high-calorie diet

liver fibrosis
- some portal and perisinusoidal fibrosis is seen in standard diet fed mice at 3 months and is increased when mice are fed the high-calorie diet

liver inflammation
- hepatic necroinflammation is not prominent, however it is aggravated after 1 month of high-calorie diet compared to standard diet and tends to alleviate with time
- non-alcoholic steatohepatitis is seen occasionally after 3 months of a standard diet and is seen in 3 of 9 mice after 3 months of the high-calorie diet

References

Additional References

Bahary N; Leibel RL; Joseph L; Friedman JM. 1990. Molecular mapping of the mouse db mutation. Proc Natl Acad Sci U S A 87(21):8642-6PubMed: 1978328 MGI: J:10819
Barinaga M. 1996. Researchers nail down leptin receptor [news; comment] Science 271(5251):913PubMed: 8584929 MGI: J:31488
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):491-5PubMed: 8608603 MGI: 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):994-6PubMed: 8584938 MGI: J:31419
Coleman DL. 1978. Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14(3):141-8PubMed: 350680 MGI: J:5986
Coleman DL; Hummel KP. 1973. The influence of genetic background on the expression of the obese (Ob) gene in the mouse. Diabetologia 9(4):287-93PubMed: 4588246 MGI: J:5400
Fiedorek FT Jr; Kay ES. 1994. Mapping of PCR-based markers for mouse chromosome 4 on a backcross penetrant for the misty (m) mutation. Mamm Genome 5(8):479-85PubMed: 7949731 MGI: J:20039
Hummel KP; Dickie MM; Coleman DL. 1966. Diabetes, a new mutation in the mouse. Science 153(740):1127-8PubMed: 5918576 MGI: J:5010
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):2007-13PubMed: 8182132 MGI: J:17991
Leiter EH; Chapman HD; Coleman DL. 1989. The influence of genetic background on the expression of mutations at the diabetes locus in the mouse. V. Interaction between the db gene and hepatic sex steroid sulfotransferases correlates with gender-dependent susceptibility to hyperglycemia. Endocrinology 124(2):912-22PubMed: 2912706 MGI: J:26013
Sviderskaya EV; Novak EK; Swank RT; Bennett DC. 1998. The murine misty mutation: phenotypic effects on melanocytes, platelets and brown fat. Genetics 148(1):381-90PubMed: 9475748 MGI: J:45425
Trayhurn P. 1979. Thermoregulation in the diabetic-obese (db/db) mouse. The role of non-shivering thermogenesis in energy balance. Pflugers Arch 380(3):227-32PubMed: 573463 MGI: J:6202
Truett GE; Tempelman RJ; Walker JA; Wilson JK. 1998. Misty (m) affects growth traits. Am J Physiol 275(1 Pt 2):R29-32PubMed: 9688956 MGI: J:48831

Additional - Dock7^m related

Additional - Lepr^db related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Restriction Enzyme Digest:Lepr
- Pyrosequencing:Lepr
- End Point Analysis:Lepr
- Genotyping resources and troubleshooting
Citation
When using the B6-diabetes mouse strain in a publication, please cite the originating article(s) and include JAX stock #000699 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous, Heterozygous or Wild-type for Dock7<m> Lepr<db>

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Dock7<m> Lepr<db>/+ +/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.Cg-Dock7<m> Lepr<db>/+ +/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.Cg-Dock7<m> Lepr<db>/+ +/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.Cg-Dock7<m> Lepr<db>/+ +/J Frozen Embryos	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:B6-diabetes

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Dock7m

Allele Symbol: Dock7m

Leprdb

Allele Symbol: Leprdb

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: Leprdb related

Genotype: Dock7m related

Mammalian Phenotype Terms by Genotype

Genotype: Leprdb/Leprdbinvolves: C57BLKS/J

adipose tissue phenotype

cardiovascular system phenotype

nervous system phenotype

renal/urinary system phenotype

reproductive system phenotype

vision/eye phenotype

cellular phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

behavior/neurological phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

mortality/aging

muscle phenotype

Genotype: Leprdb/LeprdbC57BLKS/J-Lepr

behavior/neurological phenotype

homeostasis/metabolism phenotype

cardiovascular system phenotype

liver/biliary system phenotype

renal/urinary system phenotype

growth/size/body region phenotype

Genotype: Leprdb/LeprdbFVB.BKS-Lepr

endocrine/exocrine gland phenotype

renal/urinary system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: Leprdb/LeprdbBKS.Cg-Dock7 +/+ Lepr/J

behavior/neurological phenotype

cellular phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

muscle phenotype

nervous system phenotype

renal/urinary system phenotype

vision/eye phenotype

cardiovascular system phenotype

Genotype: Leprdb/Lepr+B6.Cg-Dock7 +/+ Lepr/J

growth/size/body region phenotype

mortality/aging

Genotype: Leprdb/LeprdbBKS.Cg-Dock7 +/+ Lepr/OlaHsd

digestive/alimentary phenotype

immune system phenotype

liver/biliary system phenotype

Genotype: Leprdb/Lepr+involves: C57BLKS/J

adipose tissue phenotype

homeostasis/metabolism phenotype

behavior/neurological phenotype

cellular phenotype

embryo phenotype

growth/size/body region phenotype

Genotype: Dock7m/Dock7+ Leprdb/Lepr+BKS.Cg-Dock7 +/+ Lepr/J

mortality/aging

Genotype: Leprdb/Leprdbinvolves: 129S2/SvPas * C57BL/6 * C57BLKS/J

renal/urinary system phenotype

Genotype: Leprdb/LeprdbBKS.Cg-Dock7 +/+ Lepr/Jcl

adipose tissue phenotype

Dock7^m

Allele Symbol: Dock7^m

Lepr^db

Allele Symbol: Lepr^db

Genotype: Lepr^db related

Genotype: Dock7^m related

Genotype: Lepr^db/Lepr^db
involves: C57BLKS/J

Genotype: Lepr^db/Lepr^db
C57BLKS/J-Lepr

Genotype: Lepr^db/Lepr^db
FVB.BKS-Lepr

Genotype: Lepr^db/Lepr^db
BKS.Cg-Dock7 +/+ Lepr/J

Genotype: Lepr^db/Lepr⁺
B6.Cg-Dock7 +/+ Lepr/J

Genotype: Lepr^db/Lepr^db
BKS.Cg-Dock7 +/+ Lepr/OlaHsd

Genotype: Lepr^db/Lepr⁺
involves: C57BLKS/J

Genotype: Dock7^m/Dock7⁺ Lepr^db/Lepr⁺
BKS.Cg-Dock7 +/+ Lepr/J

Genotype: Lepr^db/Lepr^db
involves: 129S2/SvPas * C57BL/6 * C57BLKS/J

Genotype: Lepr^db/Lepr^db
BKS.Cg-Dock7 +/+ Lepr/Jcl

Genotype: Lepr^db/Lepr^db
B6.BKS(D)-Lepr/J

Genotype: Lepr^db/Lepr^db
B6.Cg-Dock7 +/+ Lepr/J

Genotype: Lepr^db/Lepr^db
B6.BKS(D)-Lepr/JOrlRj

Additional - Dock7^m related

Additional - Lepr^db related