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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Leprdb
diabetes
MGI:1856009
Summary 36 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Leprdb/Leprdb B6.BKS(D)-Leprdb/J MGI:4429457
hm2
Leprdb/Leprdb B6.Cg-Dock7m +/+ Leprdb/J MGI:3689720
hm3
Leprdb/Leprdb BKS.Cg-Dock7m +/+ Leprdb/J MGI:3694548
hm4
Leprdb/Leprdb BKS.Cg-Dock7m +/+ Leprdb/Jcl MGI:4418957
hm5
Leprdb/Leprdb BKS.Cg-Dock7m +/+ Leprdb/OlaHsd MGI:3774345
hm6
Leprdb/Leprdb C57BLKS/J MGI:2663174
hm7
Leprdb/Leprdb FVB.BKS-Leprdb MGI:3655832
hm8
Leprdb/Leprdb involves: 129S2/SvPas * C57BL/6 * C57BLKS/J MGI:3803206
hm9
Leprdb/Leprdb involves: C57BL/6 MGI:3774853
hm10
Leprdb/Leprdb involves: C57BL/6 * C57BLKS/J MGI:3822315
hm11
Leprdb/Leprdb involves: C57BLKS/J MGI:2654708
ht12
Leprdb/Lepr+ B6.Cg-Dock7m +/+ Leprdb/J MGI:3697525
ht13
Leprdb/Lepr+ BKS.Cg-Dock7m +/+ Leprdb/J MGI:3776095
ht14
Leprdb/Lepr+ involves: C57BLKS/J MGI:3774843
ht15
Leprdb/Leprdb-5J involves: C57BLKS/J * NOD/ShiLtJ MGI:3699233
cn16
Cebpbtm1.1Maka/Cebpbtm1.1Maka
Leprdb/Leprdb
Tg(Ins2-cre)23Herr/0
involves: 129P2/OlaHsd * C57BL/6J * C57BLKS/J * CBA/J MGI:4421499
cn17
Leprdb/Leprdb
Ptentm1Hwu/Ptentm1Hwu
Tg(Ins2-cre)25Mgn/0
involves: 129S4/SvJae * C57BL/6 * C57BLKS/J * DBA MGI:5013485
cx18
Foxo1tm2.1Dac/Foxo1tm2.1Dac
Leprdb/Leprdb
B6.Cg-Foxo1tm2.1Dac Leprdb MGI:5305587
cx19
Leprdb/Leprdb
Nos3tm1Unc/Nos3tm1Unc
BKS.Cg-Leprdb Nos3tm1Unc MGI:4361710
cx20
Apoetm1Unc/Apoetm1Unc
Leprdb/Leprdb
involves: 129P2/OlaHsd * C57BLKS/J MGI:3775795
cx21
Leprdb/Leprdb
Plin1tm1Chan/Plin1tm1Chan
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BLKS/J MGI:3839678
cx22
Gdf15tm1Sjl/Gdf15tm1Sjl
Leprdb/Leprdb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BLKS/J MGI:5548175
cx23
Aqp9tm1Nlsn/Aqp9tm1Nlsn
Leprdb/Leprdb
involves: 129S1/Sv * C57BL/6 * C57BLKS/J MGI:3720617
cx24
Leprdb/Leprdb
Serpine1tm1Mlg/Serpine1tm1Mlg
involves: 129S2/SvPas * C57BL/6 * C57BLKS/J MGI:3803207
cx25
Leprdb/Leprdb
Rock1tm1Leiw/Rock1tm1Leiw
involves: 129S7/SvEvBrd * C57BLKS/J * FVB/N MGI:5316083
cx26
Leprdb/Lepr+
Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H * C57BL/6 * C57BLKS/J MGI:5435319
cx27
Dbsq1BKS/Dbsq1BKS
Leprdb/Leprdb
involves: C3H/HeJ * C57BLKS MGI:3693603
cx28
Dbsq1BKS/Dbsq1C3H/HeJ
Leprdb/Leprdb
involves: C3H/HeJ * C57BLKS MGI:3693604
cx29
Dbsq2C3H/HeJ/Dbsq2C3H/HeJ
Leprdb/Lepr+
involves: C3H/HeJ * C57BLKS MGI:3693605
cx30
Dbsq2BKS/Dbsq2C3H/HeJ
Leprdb/Lepr+
involves: C3H/HeJ * C57BLKS MGI:3693606
cx31
Dbsq3C3H/HeJ/Dbsq3C3H/HeJ
Leprdb/Lepr+
involves: C3H/HeJ * C57BLKS MGI:3693607
cx32
Dbsq3BKS/Dbsq3C3H/HeJ
Leprdb/Lepr+
involves: C3H/HeJ * C57BLKS MGI:3693608
cx33
Ccr2tm1.1(CCR2)Rodb/Ccr2tm1.1(CCR2)Rodb
Leprdb/Leprdb
involves: C57BL/6 * C57BLKS/J MGI:5552736
cx34
Leprdb/Leprdb
Tg(Fabp4-Fcor)1Jnak/0
involves: C57BL/6 * C57BLKS/J * DBA/2 MGI:5427610
cx35
Cdkn1btm1Kin/Cdkn1b+
Leprdb/Leprdb
involves: C57BL/6J * C57BLKS/J MGI:3529778
cx36
Cdkn1btm1Kin/Cdkn1btm1Kin
Leprdb/Leprdb
involves: C57BL/6J * C57BLKS/J MGI:3529774


Genotype
MGI:4429457
hm1
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
B6.BKS(D)-Leprdb/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• mice treated with leptin fail to exhibit a decrease in food intake unlike similarly treated wild-type mice (J:166105)
• mice treated with leptin fail to exhibit a decrease in food intake unlike similarly treated wild-type mice (J:166105)

behavior/neurological
• faster in food finding trials relative to controls (J:112820)
• faster in food finding trials relative to controls (J:112820)
• during the dark phase (J:166105)
• during the dark phase (J:166105)

renal/urinary system
• homozygotes develop significant glomerulosclerosis by 18 weeks of age (J:160943)
• homozygotes develop significant glomerulosclerosis by 18 weeks of age (J:160943)




Genotype
MGI:3689720
hm2
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
B6.Cg-Dock7m +/+ Leprdb/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• increase in body weight becomes apparent at 4-6 weeks of age (J:18161)
• increase in body weight becomes apparent at 4-6 weeks of age (J:18161)
• body weight is 2- to 3-fold more than in wild-type mice by 10 weeks of age (J:82334)
• body weight is 10% and 20% more in males and females, respectively, compared to Leprrtm1Mgmj homozygotes (J:82334)
• body weight is 2- to 3-fold more than in wild-type mice by 10 weeks of age (J:82334)
• body weight is 10% and 20% more in males and females, respectively, compared to Leprrtm1Mgmj homozygotes (J:82334)
• develop progressive obesity (J:103063)
• develop progressive obesity (J:103063)
• snout to anus length is decreased by about 5% compared to wild-type mice (J:82334)
• snout to anus length is decreased by about 5% compared to wild-type mice (J:82334)

behavior/neurological

cardiovascular system
• exhibit myocyte hypertrophy (J:103063)
• exhibit myocyte 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 (J:103063)
• induced weight loss via leptin infusion, but not via caloric restriction, partially resolves the 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 (J:103063)
• induced weight loss via leptin infusion, but not via caloric restriction, partially resolves the hypertrophy (J:103063)

muscle
• exhibit myocyte hypertrophy (J:103063)
• exhibit myocyte hypertrophy (J:103063)

homeostasis/metabolism
• HDL cholesterol and glucose levels increase concurrently (J:18161)
• 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 (J:18161)
• HDL cholesterol and glucose levels increase concurrently (J:18161)
• 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 (J:18161)
• fasting plasma total cholesterol concentration is increased 2 fold over controls (J:18161)
• fasting plasma total cholesterol concentration is increased 2 fold over controls (J:18161)
• triglyceride levels are elevated 1.5- to 2-fold (J:18161)
• triglyceride levels are elevated 1.5- to 2-fold (J:18161)
• female mice exhibit an increase in hypothalamic gonadotrophin releasing hormone compared to in wild-type mice (J:6157)
• female mice exhibit an increase in hypothalamic gonadotrophin releasing hormone compared to in wild-type mice (J:6157)
• decreased in serum (J:115772)
• decreased in serum (J:115772)
• elevated levels of eotaxin, keratinocyte cytokine, and monocyte chemotactic protein-1 (also elevated in serum) in bronchoalveolar lavage fluid (J:115772)
• elevated levels of eotaxin, keratinocyte cytokine, and monocyte chemotactic protein-1 (also elevated in serum) in bronchoalveolar lavage fluid (J:115772)
• elevated levels of IL-6 in bronchoalveolar lavage fluid (J:115772)
• elevated levels of IL-6 in bronchoalveolar lavage fluid (J:115772)
• elevated levels of IL-6 in serum (J:115772)
• elevated levels of IL-6 in serum (J:115772)

reproductive system
• atrophy of the reproductive organs (J:82334)
• atrophy of the reproductive organs (J:82334)
(J:6157)
(J:6157)
(J:6157)
(J:6157)
(J:82334)
(J:82334)
• females never show signs of vaginal oestrous (J:82334)
• females never show signs of vaginal oestrous (J:82334)
• mice exhibit diestrous vaginal acyclicity or occasional metestrous acyclicity (J:6157)
• mice exhibit diestrous vaginal acyclicity or occasional metestrous acyclicity (J:6157)
(J:6157)
(J:6157)
• all females fail to reproduce (J:82334)
• all females fail to reproduce (J:82334)

respiratory system
• elevated levels of eotaxin, Il6, keratinocyte cytokine, monocyte chemotactic protein-1, and neutrophiles in bronchoalveolar lavage as a result of ozone exposure (J:115772)
• ozone induces significantly elevated levels of TNFR1 (J:115772)
• ozone induces a nonsignificant elevation of TNFR2 levels (J:115772)
• elevated pulmonary levels of Il1beta mRNA 24 hours after ozone exposure (J:115772)
• elevated pulmonary levels of TNF mRNA 24 hours after ozone exposure but to a lesser extent than in controls (J:115772)
• elevated levels of eotaxin, Il6, keratinocyte cytokine, monocyte chemotactic protein-1, and neutrophiles in bronchoalveolar lavage as a result of ozone exposure (J:115772)
• ozone induces significantly elevated levels of TNFR1 (J:115772)
• ozone induces a nonsignificant elevation of TNFR2 levels (J:115772)
• elevated pulmonary levels of Il1beta mRNA 24 hours after ozone exposure (J:115772)
• elevated pulmonary levels of TNF mRNA 24 hours after ozone exposure but to a lesser extent than in controls (J:115772)
• reduced (J:115772)
• pressure volume curves shifted to the right (J:115772)
• reduced (J:115772)
• pressure volume curves shifted to the right (J:115772)
• end-expiratory pause increases considerably less than in controls after ozone exposure (J:115772)
• end-expiratory pause increases considerably less than in controls after ozone exposure (J:115772)
• total lung resistance increases much more in response to ozone than in control mice (J:115772)
• responsiveness to methacholine and serotonin is much greater than controls (J:115772)
• total lung resistance increases much more in response to ozone than in control mice (J:115772)
• responsiveness to methacholine and serotonin is much greater than controls (J:115772)
• ventilation volumes decline with ozone exposure but to a lesser degree than for controls (J:115772)
• ventilation volumes decline with ozone exposure but to a lesser degree than for controls (J:115772)

immune system
• increased numbers in bronchoalveolar lavage (J:115772)
• increased numbers in bronchoalveolar lavage (J:115772)
• decrease blood leukocyte numbers (J:115772)
• decrease blood leukocyte numbers (J:115772)
• elevated levels of eotaxin, keratinocyte cytokine, and monocyte chemotactic protein-1 (also elevated in serum) in bronchoalveolar lavage fluid (J:115772)
• elevated levels of eotaxin, keratinocyte cytokine, and monocyte chemotactic protein-1 (also elevated in serum) in bronchoalveolar lavage fluid (J:115772)
• elevated levels of IL-6 in bronchoalveolar lavage fluid (J:115772)
• elevated levels of IL-6 in bronchoalveolar lavage fluid (J:115772)
• elevated levels of IL-6 in serum (J:115772)
• elevated levels of IL-6 in serum (J:115772)
• elevated levels of eotaxin, Il6, keratinocyte cytokine, monocyte chemotactic protein-1, and neutrophiles in bronchoalveolar lavage as a result of ozone exposure (J:115772)
• ozone induces significantly elevated levels of TNFR1 (J:115772)
• ozone induces a nonsignificant elevation of TNFR2 levels (J:115772)
• elevated pulmonary levels of Il1beta mRNA 24 hours after ozone exposure (J:115772)
• elevated pulmonary levels of TNF mRNA 24 hours after ozone exposure but to a lesser extent than in controls (J:115772)
• elevated levels of eotaxin, Il6, keratinocyte cytokine, monocyte chemotactic protein-1, and neutrophiles in bronchoalveolar lavage as a result of ozone exposure (J:115772)
• ozone induces significantly elevated levels of TNFR1 (J:115772)
• ozone induces a nonsignificant elevation of TNFR2 levels (J:115772)
• elevated pulmonary levels of Il1beta mRNA 24 hours after ozone exposure (J:115772)
• elevated pulmonary levels of TNF mRNA 24 hours after ozone exposure but to a lesser extent than in controls (J:115772)

tumorigenesis
• increased metastasis to the lung of both melanoma cell lines and lung cancer cell lines initially injected in the tail vein (J:117826)
• increased metastasis to the lung of both melanoma cell lines and lung cancer cell lines initially injected in the tail vein (J:117826)

hematopoietic system
• increased numbers in bronchoalveolar lavage (J:115772)
• increased numbers in bronchoalveolar lavage (J:115772)
• decrease blood leukocyte numbers (J:115772)
• decrease blood leukocyte numbers (J:115772)

nervous system

Mouse Models of Human Disease
OMIM ID Ref(s)
Obesity 601665 J:18161 , J:82234 , J:103063




Genotype
MGI:3694548
hm3
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
BKS.Cg-Dock7m +/+ Leprdb/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• increased secreation of glucagon by pancreatic cells in culture (J:6264)
• increased secreation of glucagon by pancreatic cells in culture (J:6264)
• brain derived neurotrophic factor (BDNF) causes a drop in blood glucose relative to controls 8 weeks after treatment (J:43162)
• affect of BDNF on blood glucose becomes progressively less as mice age (J:43162)
• neurotrophin 3 also causes a drop in blood glucose but the glucose levels return to normal by 24 hours after treatment (J:43162)
• brain derived neurotrophic factor (BDNF) causes a drop in blood glucose relative to controls 8 weeks after treatment (J:43162)
• affect of BDNF on blood glucose becomes progressively less as mice age (J:43162)
• neurotrophin 3 also causes a drop in blood glucose but the glucose levels return to normal by 24 hours after treatment (J:43162)
• glucose levels are reduced at all times tested when mice are placed on feeding restriction during the dark phase (J:91813)
• glucose levels are reduced at all times tested when mice are placed on feeding restriction during the dark phase (J:91813)
• blood glucose shows a progressive increase from 5 through 33 weeks (J:6323)
• blood glucose shows a progressive increase from 5 through 33 weeks (J:6323)
• fasting blood glucose level is significantly higher than control at 26 weeks of age (J:135864)
• fasting blood glucose level is significantly higher than control at 26 weeks of age (J:135864)
• BDNF causes a 50% reduction in plasma insulin relative to controls (J:43162)
• BDNF causes a 50% reduction in plasma insulin relative to controls (J:43162)
• morning insulin levels lowered when feeding is restricted during the dark phase (J:91813)
• morning insulin levels lowered when feeding is restricted during the dark phase (J:91813)
• 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 (J:18161)
• 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 (J:18161)
• fasting plasma total cholesterol concentration is increased 2 fold over controls (J:18161)
• fasting plasma total cholesterol concentration is increased 2 fold over controls (J:18161)
• triglyceride levels are reduced at all times tested when mice are placed on feeding restriction during the dark phase (J:91813)
• triglyceride levels are reduced at all times tested when mice are placed on feeding restriction during the dark phase (J:91813)
• triglyceride levels are elevated 1.5- to 2-fold (J:18161)
• triglyceride levels are elevated 1.5- to 2-fold (J:18161)
• BDNF treatment causes a lower blood glucose level response in a glucose tolerance test (J:43162)
• BDNF treatment causes a lower blood glucose level response in a glucose tolerance test (J:43162)
• in diabetic wounds, PGE2 level is consistently less than 50% of wild-type wounds at all times (J:185546)
• in diabetic wounds, PGE2 level is consistently less than 50% of wild-type wounds at all times (J:185546)
• 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) (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) (J:82491)
• moderate albuminuria is observed at 26 weeks of age (J:135864)
• moderate albuminuria is observed at 26 weeks of age (J:135864)
• wound healing is impaired, with an average wound closure time of 22 days, 7 days longer than in controls (J:185546)
• 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 (J:185546)
• wound healing is impaired, with an average wound closure time of 22 days, 7 days longer than in controls (J:185546)
• 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 (J:185546)

growth/size/body
• body weight drops after 6 days on feeding restriction during the dark phase (J:91813)
• body weight drops after 6 days on feeding restriction during the dark phase (J:91813)
• become progressively obese starting at 5 weeks of age (J:6323)
• weight reaches 2.5X that of control mice by 3 months of age (J:6323)
• become progressively obese starting at 5 weeks of age (J:6323)
• weight reaches 2.5X that of control mice by 3 months of age (J:6323)

renal/urinary system
• 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) (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) (J:82491)
• moderate albuminuria is observed at 26 weeks of age (J:135864)
• moderate albuminuria is observed at 26 weeks of age (J:135864)
• moderate mesangial expansion is observed in glomeruli at 26 weeks (J:135864)
• moderate mesangial expansion is observed in glomeruli at 26 weeks (J:135864)
• 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) (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) (J:82491)

nervous system
• axonal growth cone extension fails to occur for neurons treated in culture with 100ng/ml of leptin (J:112680)
• axonal growth cone extension fails to occur for neurons treated in culture with 100ng/ml of leptin (J:112680)
• myelinated fibers reduced in numbers at 25 weeks in the sural nerve (J:6323)
• unmyelinated fibers reduced in numbers at 25 weeks in the vagus nerve (J:6323)
• myelinated fiber density increases in most nerves (not the peroneal and phrenic nerves) (J:6323)
• unmyelinated fiber density increase in the sural, peroneal, and vagus nerves (J:6323)
• myelinated fibers reduced in numbers at 25 weeks in the sural nerve (J:6323)
• unmyelinated fibers reduced in numbers at 25 weeks in the vagus nerve (J:6323)
• myelinated fiber density increases in most nerves (not the peroneal and phrenic nerves) (J:6323)
• unmyelinated fiber density increase in the sural, peroneal, and vagus nerves (J:6323)
• non significant shift toward smaller fiber diameter at 15 weeks of age (J:6323)
• significantly shifted to smaller diameter fibers by 25 weeks in ventral roots, dorsal roots, sural nerve (J:6323)
• smaller diameter nerve fibers in peroneal, phrenic and vagus nerves at 25 weeks but not significant (J:6323)
• small numbers of very large unmyelinated fibers (up to 1.6 micrometers) (J:6323)
• shift of unmyelinated fibers to smaller diameters (J:6323)
• non significant shift toward smaller fiber diameter at 15 weeks of age (J:6323)
• significantly shifted to smaller diameter fibers by 25 weeks in ventral roots, dorsal roots, sural nerve (J:6323)
• smaller diameter nerve fibers in peroneal, phrenic and vagus nerves at 25 weeks but not significant (J:6323)
• small numbers of very large unmyelinated fibers (up to 1.6 micrometers) (J:6323)
• shift of unmyelinated fibers to smaller diameters (J:6323)
• number of myelin lamellae relative to nerve diameter is increased (J:6323)
• number of myelin lamellae relative to nerve diameter is increased (J:6323)
• motor nerve conductance significantly lower than controls from 7 weeks of age onward (J:6323)
• velocity returns to and is maintained at prediabetic levels by 15 weeks of age whereas control mice show a continuous increase in velocity (J:6323)
• insulin treatment results in improved conductance but only for the duration of treatment and control levels of conductance are never restored (J:6323)
• no conductance improvement is seen in mice over 23 weeks in age due to insulin treatment (J:6323)
• motor nerve conductance significantly lower than controls from 7 weeks of age onward (J:6323)
• velocity returns to and is maintained at prediabetic levels by 15 weeks of age whereas control mice show a continuous increase in velocity (J:6323)
• insulin treatment results in improved conductance but only for the duration of treatment and control levels of conductance are never restored (J:6323)
• no conductance improvement is seen in mice over 23 weeks in age due to insulin treatment (J:6323)
• CA1 hippocampal slices indicate brief post tetanic potentiation but no long term potentiation on recordings of excitatory post-synaptic potentials (J:109401)
• CA1 hippocampal slices indicate brief post tetanic potentiation but no long term potentiation on recordings of excitatory post-synaptic potentials (J:109401)
• CA1 hippocampal slices indicate no long term depression on recordings of excitatory post-synaptic potentials (J:109401)
• CA1 hippocampal slices indicate no long term depression on recordings of excitatory post-synaptic potentials (J:109401)

behavior/neurological
• daily locomotor pattern becomes attenuated in 6-8 week old mice but rhythmicity is retained (J:91813)
• daily locomotor activity rhythmicity severely diminished at 13-14 weeks, 75% fail to show significant rhythmicity (J:91813)
• daily locomotor rhythmicity restored by feeding restriction during dark phase (J:91813)
• daily locomotor pattern becomes attenuated in 6-8 week old mice but rhythmicity is retained (J:91813)
• daily locomotor activity rhythmicity severely diminished at 13-14 weeks, 75% fail to show significant rhythmicity (J:91813)
• daily locomotor rhythmicity restored by feeding restriction during dark phase (J:91813)
• food intake is about 60% of control level (J:43162)
• food intake is about 60% of control level (J:43162)
• longer swimming distances than control mice in a Morris water maze test (J:109401)
• longer swimming distances than control mice in a Morris water maze test (J:109401)
• cross the original platform location less frequently than do controls in a Morris water maze test (J:109401)
• cross the original platform location less frequently than do controls in a Morris water maze test (J:109401)

vision/eye
• prolonged latency of the b-wave in the retina (J:103714)
• delays in oscillatory potentials 1, 2, 3 although only the delay in "OP1" is significant (J:103714)
• prolonged latency of the b-wave in the retina (J:103714)
• delays in oscillatory potentials 1, 2, 3 although only the delay in "OP1" is significant (J:103714)

endocrine/exocrine glands
• increased secreation of glucagon by pancreatic cells in culture (J:6264)
• increased secreation of glucagon by pancreatic cells in culture (J:6264)

cardiovascular system
• dense bodies found in the smooth muscle of intramyocardial arteries (J:6115)
• dense bodies found in the smooth muscle of intramyocardial arteries (J:6115)
• presence of many lipid droplets (J:6115)
• dense bodies present in places normally occupied by mitochondria (J:6115)
• disrupted sarcomeres sometimes (J:6115)
• presence of many lipid droplets (J:6115)
• dense bodies present in places normally occupied by mitochondria (J:6115)
• disrupted sarcomeres sometimes (J:6115)

muscle
• presence of many lipid droplets (J:6115)
• dense bodies present in places normally occupied by mitochondria (J:6115)
• disrupted sarcomeres sometimes (J:6115)
• presence of many lipid droplets (J:6115)
• dense bodies present in places normally occupied by mitochondria (J:6115)
• disrupted sarcomeres sometimes (J:6115)

cellular
• axonal growth cone extension fails to occur for neurons treated in culture with 100ng/ml of leptin (J:112680)
• axonal growth cone extension fails to occur for neurons treated in culture with 100ng/ml of leptin (J:112680)




Genotype
MGI:4418957
hm4
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
BKS.Cg-Dock7m +/+ Leprdb/Jcl
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Increased beta cell mass in Leprdb/Leprdb mice and Leprdb/Leprdb Cebpbtm1.1Maka/Cebpbtm1.1Maka Tg(Ins2-cre)23Herr/0 mice

endocrine/exocrine glands
• at 8 weeks, pancreatic islet cell proliferation is increased compared to in heterozygous mice (J:156725)
• however, pancreatic islet cell proliferation by 16 weeks is normal (J:156725)
• at 8 weeks, pancreatic islet cell proliferation is increased compared to in heterozygous mice (J:156725)
• however, pancreatic islet cell proliferation by 16 weeks is normal (J:156725)
• pancreatic islet cell apoptosis is increased compared to in heterozygous mice (J:156725)
• pancreatic islet cell apoptosis is increased compared to in heterozygous mice (J:156725)

homeostasis/metabolism

adipose tissue
• the epididymal fat pad exhibits macrophage infiltration unlike in wild-type mice (J:110277)
• the epididymal fat pad exhibits macrophage infiltration unlike in wild-type mice (J:110277)

cellular
• pancreatic islet cell apoptosis is increased compared to in heterozygous mice (J:156725)
• pancreatic islet cell apoptosis is increased compared to in heterozygous mice (J:156725)




Genotype
MGI:3774345
hm5
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
BKS.Cg-Dock7m +/+ Leprdb/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• reduced levels of occludin in intestinal sections (J:124815)
• zonula occludens 1 has a discontinuous distribution (J:124815)
• reduced levels of occludin in intestinal sections (J:124815)
• zonula occludens 1 has a discontinuous distribution (J:124815)
• transepithelial resistance in the epithelium is reduced, indictive of a disrupted mucosal barrier function (J:124815)
• transepithelial resistance in the epithelium is reduced, indictive of a disrupted mucosal barrier function (J:124815)

immune system
• increased release of monocyte chemo attractant protein by hepatic stellate cells (J:124815)
• increased release of monocyte chemo attractant protein by hepatic stellate cells (J:124815)
• increased release by hepatic stellate cells (J:124815)
• increased release by hepatic stellate cells (J:124815)
• higher levels of endotoxin are found in portal blood (entotoxemia) (J:124815)
• higher levels of endotoxin are found in portal blood (entotoxemia) (J:124815)
• increased succeptibility of hepatic stellate cells to LPS (J:124815)
• increased succeptibility of hepatic stellate cells to LPS (J:124815)

liver/biliary system




Genotype
MGI:2663174
hm6
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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 (J:104790)
• 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 (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 (J:104790)
• 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 (J:104790)

behavior/neurological

endocrine/exocrine glands
• islet mass and density are significantly increased compared to wild-type mice (J:96047)
• islet mass and density are significantly increased compared to wild-type mice (J:96047)
• individual beta cell size is increased (J:96047)
• individual beta cell size is increased (J:96047)

growth/size/body
• overweight by 4 weeks of age (J:106597)
• overweight by 4 weeks of age (J:106597)

homeostasis/metabolism
• 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 (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 (J:104790)
• significant increase in the percentage of plasma glycosylated hemoglobin (J:104790)
• significant increase in the percentage of plasma glycosylated hemoglobin (J:104790)
• diabetic phenotype appears earlier in males than in females (J:107138)
• diabetic phenotype appears earlier in males than in females (J:107138)
• by 8 weeks (J:106597)
• by 8 weeks (J:106597)
• hyperinsulinemia by 8 weeks (J:106597)
• hyperinsulinemia by 8 weeks (J:106597)

cardiovascular system
• myocardial triacylglycerol content 2X that of controls at 10-18 weeks of age (J:107138)
• myocardial triacylglycerol content 2X that of controls at 10-18 weeks of age (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 (J:106871)
• 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 (J:106871)
• reduced aortic flow (J:107138)
• reduced aortic flow (J:107138)
• cardiac output is reduced in fatty acid perfused hearts (J:106871)
• cardiac output is reduced in fatty acid perfused hearts (J:106871)
• reduced recovery of mechanical function after 13 minutes of ischemia and reperfusion (J:107138)
• reduced recovery of mechanical function after 13 minutes of ischemia and reperfusion (J:107138)
• hypercontractility of smooth muscle in aortic strips due to either phenylephrine or serotonin (J:106597)
• hypercontractility corrollated with the levels of obesity, hyperglycemia, and hyperinsulinemia (J:106597)
• maximal contractions increase with age rather than decrease as in controls (J:106597)
• hypercontractility of smooth muscle in aortic strips due to either phenylephrine or serotonin (J:106597)
• hypercontractility corrollated with the levels of obesity, hyperglycemia, and hyperinsulinemia (J:106597)
• maximal contractions increase with age rather than decrease as in controls (J:106597)
• 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 (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 (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 (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 (J:106871)
• intrinsic heart rates are reduced at all workloads (J:106871)
• intrinsic heart rates are reduced at all workloads (J:106871)
• decreased peak systolic pressure (J:107138)
• decreased peak systolic pressure X cardiac output (J:107138)
• decreased peak systolic pressure X heart rate (J:107138)
• decreased peak systolic pressure (J:107138)
• decreased peak systolic pressure X cardiac output (J:107138)
• decreased peak systolic pressure X heart rate (J:107138)
• 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 (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 (J:104790)

hematopoietic system
• significant increase in the percentage of plasma glycosylated hemoglobin (J:104790)
• significant increase in the percentage of plasma glycosylated hemoglobin (J:104790)

cellular
• elevation of fatty acids in perfused hearts causes an increase in fatty acid oxidation combined with a reduction in glucose oxidation rates (J:106871)
• elevation of fatty acids in perfused hearts causes an increase in fatty acid oxidation combined with a reduction in glucose oxidation rates (J:106871)
• carbohydrate oxidation becomes reduced (J:107138)
• palmitate oxidation is elevated (J:107138)
• carbohydrate oxidation becomes reduced (J:107138)
• palmitate oxidation is elevated (J:107138)
• state 3 respiration is elevated in cardiac mitochondria incubated with palmitoyl-carnitine but not with pyruvate (J:106871)
• state 3 respiration is elevated in cardiac mitochondria incubated with palmitoyl-carnitine but not with pyruvate (J:106871)

muscle
• hypercontractility of smooth muscle in aortic strips due to either phenylephrine or serotonin (J:106597)
• hypercontractility corrollated with the levels of obesity, hyperglycemia, and hyperinsulinemia (J:106597)
• maximal contractions increase with age rather than decrease as in controls (J:106597)
• hypercontractility of smooth muscle in aortic strips due to either phenylephrine or serotonin (J:106597)
• hypercontractility corrollated with the levels of obesity, hyperglycemia, and hyperinsulinemia (J:106597)
• maximal contractions increase with age rather than decrease as in controls (J:106597)
• 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 (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 (J:106871)




Genotype
MGI:3655832
hm7
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
FVB.BKS-Leprdb
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• mice of both sexes are obese (J:78850)
• mice of both sexes are obese (J:78850)

homeostasis/metabolism
• Background Sensitivity: after a 2-day fast on refeeding with carbohydrate-free diet, female obese mice show a rise in glucose (J:78850)
• Background Sensitivity: after a 2-day fast on refeeding with carbohydrate-free diet, female obese mice show a rise in glucose (J:78850)
• Background Sensitivity: obese mice have a prolonged period of hyperglycemia compared to obese B6.BKS-Leprdb mice where glucose levels rarely exceed 250 mg/dl (J:78850)
• fasting mice are hyperglycemic at 3 months of age, while obese B6.BKS-Leprdb fasted mice are euglycemic (J:78850)
• 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) (J:78850)
• Background Sensitivity: obese mice have a prolonged period of hyperglycemia compared to obese B6.BKS-Leprdb mice where glucose levels rarely exceed 250 mg/dl (J:78850)
• fasting mice are hyperglycemic at 3 months of age, while obese B6.BKS-Leprdb fasted mice are euglycemic (J:78850)
• 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) (J:78850)
• Background Sensitivity: 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) (J:78850)
• Background Sensitivity: 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) (J:78850)
• 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-Leprdb mice clear glucose load by 90 min (J:78850)
• Background Sensitivity: obese mice show a rapid increase of blood glucose above 400 mg/dl with diminished rate of glucose clearance (J:78850)
• 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-Leprdb mice clear glucose load by 90 min (J:78850)
• Background Sensitivity: obese mice show a rapid increase of blood glucose above 400 mg/dl with diminished rate of glucose clearance (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 (J:78850)
• at a dose of 3U/kg 6-week old mice show a diminished response to insulin (J:78850)
• circulating insulin levels in the fed state show that obese mice have exteme 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 (J:78850)
• at a dose of 3U/kg 6-week old mice show a diminished response to insulin (J:78850)
• circulating insulin levels in the fed state show that obese mice have exteme insulin resistance (J:78850)

endocrine/exocrine glands
• 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 (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 (J:78850)
• some islets in obese mice have more than 1000 cells per cross section; such islets are absent in lean mice (J:78850)
• some islets in obese mice have more than 1000 cells per cross section; such islets are absent in lean mice (J:78850)

renal/urinary system
• 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 (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 (J:78850)

Mouse Models of Human Disease
OMIM ID Ref(s)
Obesity 601665 J:78850




Genotype
MGI:3803206
hm8
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
involves: 129S2/SvPas * C57BL/6 * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• total kidney collagen is increased in females by 96% (J:127478)
• total kidney collagen is increased in females by 96% (J:127478)
• 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 (J:127478)
• 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 (J:127478)




Genotype
MGI:3774853
hm9
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• 3 fold increase in bone volume (J:60001)
• 3 fold increase in bone volume (J:60001)
• rate of new bone formation increased at both 3 and 6 months (J:60001)
• rate of new bone formation increased at both 3 and 6 months (J:60001)
• increased numbers of osteoclasts (J:60001)
• increased numbers of osteoclasts (J:60001)

hematopoietic system
• increased numbers of osteoclasts (J:60001)
• increased numbers of osteoclasts (J:60001)

immune system
• increased numbers of osteoclasts (J:60001)
• increased numbers of osteoclasts (J:60001)

cellular
• increased numbers of osteoclasts (J:60001)
• increased numbers of osteoclasts (J:60001)




Genotype
MGI:3822315
hm10
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
involves: C57BL/6 * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
(J:164339)
(J:164339)
(J:142218)
(J:142218)
(J:164339)
(J:164339)

homeostasis/metabolism
• thermoregulation in response to cold exposure is severely impaired compared to wild-type controls (J:142218)
• thermoregulation in response to cold exposure is severely impaired compared to wild-type controls (J:142218)
• oxygen consumption normalized to lean mass is increased compared to wild-type controls but oxygen consumption normalized to metabolic size is decreased compared to wild-type controls (J:142218)
• oxygen consumption normalized to lean mass is increased compared to wild-type controls but oxygen consumption normalized to metabolic size is decreased compared to wild-type controls (J:142218)

growth/size/body
• early onset obesity starting from 4 weeks of age (J:142218)
• early onset obesity starting from 4 weeks of age (J:142218)

adipose tissue

behavior/neurological
• decreased activity in both the light and dark cycle (J:142218)
• decreased activity in both the light and dark cycle (J:142218)

limbs/digits/tail

skeleton




Genotype
MGI:2654708
hm11
Allelic
Composition
Leprdb/Leprdb
Genetic
Background
involves: C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Neural-specific STAT3 deletion results in severe obesity in Stat3tm1Flv/Stat3tm1Flv Tg(Nes-cre)1Kln/0 mice similar to that seen in Leprdb/Leprdb mice

homeostasis/metabolism
• reduced neointimal area relative to controls 4 weeks after femoral artery injury (J:135034)
• vascular smooth muscle proliferation significantly reduced (J:135034)
• reduced neointimal area relative to controls 4 weeks after femoral artery injury (J:135034)
• vascular smooth muscle proliferation significantly reduced (J:135034)
• mutants become hypothermic after a 12 hour fast (J:89242)
• 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 (J:89242)
• mutants become hypothermic after a 12 hour fast (J:89242)
• 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 (J:89242)
• mice treated with adenovirus expressing Adipor1 (1.5-fold increase in liver expression), show decreased plasma glucose compared to wild-type (J:117919)
• mice treated with an adenovirus expressing Adipor2 (5-fold increase in liver expression), show decreased plasma glucose compared to wild-type (J:117919)
• mice treated with adenovirus expressing Adipor1 (1.5-fold increase in liver expression), show decreased plasma glucose compared to wild-type (J:117919)
• mice treated with an adenovirus expressing Adipor2 (5-fold increase in liver expression), show decreased plasma glucose compared to wild-type (J:117919)
• plasma fasting glucose is increased (J:89242)
• plasma fasting glucose is increased (J:89242)
• diabetes is improved after treatment with an adenovirus expressing Adipor1 or Adipor2 (J:117919)
• diabetes is improved after treatment with an adenovirus expressing Adipor1 or Adipor2 (J:117919)
• at 12 weeks (J:210493)
• at 12 weeks (J:210493)
• mice treated with an adenovirus expressing Adipor 2 show improved glucose resistance and decreased plasma insulin level (J:117919)
• mice treated with an adenovirus expressing Adipor 2 show improved glucose resistance and decreased plasma insulin level (J:117919)
• fasting insulin is increased (J:89242)
• fasting insulin is increased (J:89242)
• mice treated with an adenovirus expressing Adipor1 or Adipor 2 show improved insulin resistance (J:117919)
• mice treated with an adenovirus expressing Adipor1 or Adipor 2 show improved insulin resistance (J:117919)
• in females when compared to female controls (J:5257)
• levels of protein in urine similar in males and females but levels in males lower than in male controls (J:5257)
• in females when compared to female controls (J:5257)
• levels of protein in urine similar in males and females but levels in males lower than in male controls (J:5257)

growth/size/body
• increase in total fat content (J:89242)
• increase in total fat content (J:89242)
• by four weeks of age (J:80996)
• by four weeks of age (J:80996)
• mutants are about 5% shorter than controls (J:89242)
• mutants are about 5% shorter than controls (J:89242)

reproductive system
(J:80996)
(J:80996)
• increased volume and density of lipid inclusion vacuoles (J:80996)
• basal membrane of epithelial cells displays a folded contour at locations where lipid accumulates (J:80996)
• tissue norepinephrin levels elevated by 4 weeks of age and remain elevated (J:80996)
• increased volume and density of lipid inclusion vacuoles (J:80996)
• basal membrane of epithelial cells displays a folded contour at locations where lipid accumulates (J:80996)
• tissue norepinephrin levels elevated by 4 weeks of age and remain elevated (J:80996)
• decreased relative to controls by 4 weeks of age (J:80996)
• 1/3 normal tissue weight by 12 weeks (J:80996)
• decreased relative to controls by 4 weeks of age (J:80996)
• 1/3 normal tissue weight by 12 weeks (J:80996)

vision/eye
• modest but significant elevation of intraocular pressure (J:82879)
• modest but significant elevation of intraocular pressure (J:82879)

behavior/neurological
• aversion response is more strongly generalized from saccharin to sucrose (J:85127)
• lower aversion threshold for sucrose than in controls (J:85127)
• recovery from conditioned taste aversion is more rapid than in controls (J:85127)
• aversion response is more strongly generalized from saccharin to sucrose (J:85127)
• lower aversion threshold for sucrose than in controls (J:85127)
• recovery from conditioned taste aversion is more rapid than in controls (J:85127)

renal/urinary system
• in females when compared to female controls (J:5257)
• levels of protein in urine similar in males and females but levels in males lower than in male controls (J:5257)
• in females when compared to female controls (J:5257)
• levels of protein in urine similar in males and females but levels in males lower than in male controls (J:5257)
• basement membrane becomes thickened with age (J:5257)
• basement membrane becomes thickened with age (J:5257)
• large quantites if immunoglobulin and complement are found in the mesangium (J:30970)
• large quantites if immunoglobulin and complement are found in the mesangium (J:30970)
• eventually becomes flattened (J:5257)
• eventually becomes flattened (J:5257)
• calyceal dilation eventually develops (J:5257)
• calyceal dilation eventually develops (J:5257)

immune system
• T cells from homozygous mice but not those from heterozygous mice suppressed the beta cell response to glucose + theophylline (J:7005)
• T cells from homozygous mice but not those from heterozygous mice suppressed the beta cell response to glucose + theophylline (J:7005)

nervous system
• hypothalamic uptake of norepinephrine is decreased in males (J:1325)
• hypothalamic uptake of norepinephrine is decreased in males (J:1325)

adipose tissue
• increase in total fat content (J:89242)
• increase in total fat content (J:89242)

cardiovascular system
• reduced neointimal area relative to controls 4 weeks after femoral artery injury (J:135034)
• vascular smooth muscle proliferation significantly reduced (J:135034)
• reduced neointimal area relative to controls 4 weeks after femoral artery injury (J:135034)
• vascular smooth muscle proliferation significantly reduced (J:135034)

endocrine/exocrine glands
• beta cells exhibit DNA damage unlike control cells (J:210493)
• beta cells exhibit DNA damage unlike control cells (J:210493)




Genotype
MGI:3697525
ht12
Allelic
Composition
Leprdb/Lepr+
Genetic
Background
B6.Cg-Dock7m +/+ Leprdb/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• increased survival when totally deprived of food than wild-type controls (J:6081)
• Background Sensitivity: survival when deprived of food is not as long as when in a C57BLKsS background (J:6081)
• increased survival when totally deprived of food than wild-type controls (J:6081)
• Background Sensitivity: survival when deprived of food is not as long as when in a C57BLKsS background (J:6081)

growth/size/body
• slight but significant increase in body weight compared to wild-type mice (J:82334)
• slight but significant increase in body weight compared to wild-type mice (J:82334)




Genotype
MGI:3776095
ht13
Allelic
Composition
Leprdb/Lepr+
Genetic
Background
BKS.Cg-Dock7m +/+ Leprdb/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• increased survival when totally deprived of food than wild-type controls (J:6081)
• Background Sensitivity: survival when deprived of food is longer rhan when in a C57BL/6 background (J:6081)
• increased survival when totally deprived of food than wild-type controls (J:6081)
• Background Sensitivity: survival when deprived of food is longer rhan when in a C57BL/6 background (J:6081)




Genotype
MGI:3774843
ht14
Allelic
Composition
Leprdb/Lepr+
Genetic
Background
involves: C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• fasting glucose levels elevated 25% during pregnancy (J:71934)
• fasting glucose levels elevated 25% during pregnancy (J:71934)
• profound glucose intolerance during pregnancy (J:71934)
• glucose levels 41% higher in a glucose tolerance test at 30 and at 60 minute time points (J:71934)
• 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 (J:71934)
• profound glucose intolerance during pregnancy (J:71934)
• glucose levels 41% higher in a glucose tolerance test at 30 and at 60 minute time points (J:71934)
• 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 (J:71934)
• females exhibit impaired glucose tolerance during pregnancy (J:219658)
• both male and female heterozygous offspring have impaired glucose tolerance irrespective of maternal environment (heterozygous or wild-type mothers) (J:219658)
• females exhibit impaired glucose tolerance during pregnancy (J:219658)
• both male and female heterozygous offspring have impaired glucose tolerance irrespective of maternal environment (heterozygous or wild-type mothers) (J:219658)
• elevated placental leptin levels in pregnant females (J:71934)
• elevated placental leptin levels in pregnant females (J:71934)
• 2.2X increase in fasting insulin during pregnancy compared to a 3X increase in controls (J:71934)
• leptin treatment results in a 14% reduction in insulin levels compared to a 45% reduction in controls (J:71934)
• 2.2X increase in fasting insulin during pregnancy compared to a 3X increase in controls (J:71934)
• leptin treatment results in a 14% reduction in insulin levels compared to a 45% reduction in controls (J:71934)
• pregnant dams exhibit lower fasting insulin levels than wild-type mothers (J:219658)
• pregnant dams exhibit lower fasting insulin levels than wild-type mothers (J:219658)
• mothers exhibit higher circulating leptin levels than wild-type mothers (J:219658)
• heterozygous offspring exhibit an increase in leptin levels at 6 months of age (J:219658)
• mothers exhibit higher circulating leptin levels than wild-type mothers (J:219658)
• heterozygous offspring exhibit an increase in leptin levels at 6 months of age (J:219658)

embryogenesis
• placentas from heterozygous fetuses are larger than those of wild-type fetuses, irrespective of maternal genotype (J:219658)
• placentas from heterozygous fetuses are larger than those of wild-type fetuses, irrespective of maternal genotype (J:219658)

behavior/neurological
• food intake 11% greater than controls during pregnancy (J:71934)
• leptin treatment suppresses food intake to near control levels (J:71934)
• food intake 11% greater than controls during pregnancy (J:71934)
• leptin treatment suppresses food intake to near control levels (J:71934)

other phenotype
• 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 (J:219658)
• offspring born from heterozygous mothers with gestational diabetes have lower fasting insulin levels and worse glucose tolerance than offspring born from wild-type mothers (J:219658)
• 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 (J:219658)
• offspring born from heterozygous mothers with gestational diabetes have lower fasting insulin levels and worse glucose tolerance than offspring born from wild-type mothers (J:219658)

growth/size/body
• 20% greater adipose tissue mass during pregnancy than in controls (J:71934)
• 20% greater adipose tissue mass during pregnancy than in controls (J:71934)
• heterozygous fetuses carried by wild-type dams exhibit a 5% higher birth weight than wild-type littermates (J:219658)
• heterozygous fetuses from heterozygous mothers are 3% bigger than wild-type littermates (J:219658)
• however, wild-type pups from heterozygous mothers are no bigger than wild-type fetuses carried by wild-type mothers (J:219658)
• heterozygous fetuses carried by wild-type dams exhibit a 5% higher birth weight than wild-type littermates (J:219658)
• heterozygous fetuses from heterozygous mothers are 3% bigger than wild-type littermates (J:219658)
• however, wild-type pups from heterozygous mothers are no bigger than wild-type fetuses carried by wild-type mothers (J:219658)
• heterozygous pregnant dams are heavier than wild-type mothers at E18.5 (J:219658)
• male and female heterozygous offspring from both normal and complicated pregnancies, are heavier than wild-type littermates at 3 and 6 months of age (J:219658)
• heterozygous pregnant dams are heavier than wild-type mothers at E18.5 (J:219658)
• male and female heterozygous offspring from both normal and complicated pregnancies, are heavier than wild-type littermates at 3 and 6 months of age (J:219658)
• 33% greater maternal weight gain (J:71934)
• maternal body weight at term 24% greater than controls (J:71934)
• birth weights significantly heavier than controls and unaffected by maternal leptin treatment unlike controls where maternal leptin treatment causes a decrease in birth weights (J:71934)
• 33% greater maternal weight gain (J:71934)
• maternal body weight at term 24% greater than controls (J:71934)
• birth weights significantly heavier than controls and unaffected by maternal leptin treatment unlike controls where maternal leptin treatment causes a decrease in birth weights (J:71934)

adipose tissue
• 20% greater adipose tissue mass during pregnancy than in controls (J:71934)
• 20% greater adipose tissue mass during pregnancy than in controls (J:71934)




Genotype
MGI:3699233
ht15
Allelic
Composition
Leprdb/Leprdb-5J
Genetic
Background
involves: C57BLKS/J * NOD/ShiLtJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
Leprdb-5J mutation (1 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• 25% of offspring exhibit obesity (J:118305)
• 25% of offspring exhibit obesity (J:118305)




Genotype
MGI:4421499
cn16
Allelic
Composition
Cebpbtm1.1Maka/Cebpbtm1.1Maka
Leprdb/Leprdb
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6J * C57BLKS/J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cebpbtm1.1Maka mutation (0 available); any Cebpb mutation (3 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Increased beta cell mass in Leprdb/Leprdb mice and Leprdb/Leprdb Cebpbtm1.1Maka/Cebpbtm1.1Maka Tg(Ins2-cre)23Herr/0 mice

endocrine/exocrine glands
• pancreatic islet cell apoptosis is decreased compared to in Leprdb homozygotes (J:156725)
• pancreatic islet cell apoptosis is decreased compared to in Leprdb homozygotes (J:156725)
• compared to in Leprdb homozygotes (J:156725)
• compared to in Leprdb homozygotes (J:156725)

homeostasis/metabolism
• hyperglycemia develops more slowly and is ameliorated compared to in Leprdb homozygotes (J:156725)
• hyperglycemia develops more slowly and is ameliorated compared to in Leprdb homozygotes (J:156725)
• at 12 weeks, plasma insulin levels are increased compared to in Leprdb homozygotes and wild-type mice (J:156725)
• at 12 weeks, plasma insulin levels are increased compared to in Leprdb homozygotes and wild-type mice (J:156725)

cellular
• pancreatic islet cell apoptosis is decreased compared to in Leprdb homozygotes (J:156725)
• pancreatic islet cell apoptosis is decreased compared to in Leprdb homozygotes (J:156725)




Genotype
MGI:5013485
cn17
Allelic
Composition
Leprdb/Leprdb
Ptentm1Hwu/Ptentm1Hwu
Tg(Ins2-cre)25Mgn/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * C57BLKS/J * DBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (37 available)
Tg(Ins2-cre)25Mgn mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
N
• mutants are protected from developing diabetes, and despite severe insulin resistance, mutants remain euglycemic and show normal glucose tolerance (J:170206)
• mutants are protected from developing diabetes, and despite severe insulin resistance, mutants remain euglycemic and show normal glucose tolerance (J:170206)
• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Leprdb mice (J:170206)
• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Leprdb mice (J:170206)
• mutants exhibit a similar degree of insulin resistance as single Leprdb mice (J:170206)
• mutants exhibit a similar degree of insulin resistance as single Leprdb mice (J:170206)

growth/size/body
• mutants exhibit a similar degree of weight gain as single homozygous Leprdb mice (J:170206)
• mutants exhibit a similar degree of weight gain as single homozygous Leprdb mice (J:170206)

endocrine/exocrine glands
• islets show similar degrees of hypertrophy and proliferation as those in single homozygous Leprdb mice and do not show a further increase in beta-cell mass compared to the single Leprdb mice (J:170206)
• islets show similar degrees of hypertrophy and proliferation as those in single homozygous Leprdb mice and do not show a further increase in beta-cell mass compared to the single Leprdb mice (J:170206)
• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Leprdb mice (J:170206)
• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Leprdb mice (J:170206)




Genotype
MGI:5305587
cx18
Allelic
Composition
Foxo1tm2.1Dac/Foxo1tm2.1Dac
Leprdb/Leprdb
Genetic
Background
B6.Cg-Foxo1tm2.1Dac Leprdb
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo1tm2.1Dac mutation (0 available); any Foxo1 mutation (7 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• in fasted mice (J:179687)
• in fasted mice (J:179687)




Genotype
MGI:4361710
cx19
Allelic
Composition
Leprdb/Leprdb
Nos3tm1Unc/Nos3tm1Unc
Genetic
Background
BKS.Cg-Leprdb Nos3tm1Unc
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
Nos3tm1Unc mutation (6 available); any Nos3 mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• albumin/creatinine ratio (ACR) is significantly higher than all controls (J:135864)
• albumin/creatinine ratio (ACR) is significantly higher than all controls (J:135864)
• arteriolar hyalinosis (J:135864)
• arteriolar hyalinosis (J:135864)
• glomerular basement membrane is markedly thickened by 16 weeks in comparison to all controls (J:135864)
• glomerular basement membrane is markedly thickened by 16 weeks in comparison to all controls (J:135864)
• glomerular injury is significantly increased by 24-26 weeks in comparison to all controls (J:135864)
• glomerular injury is significantly increased by 24-26 weeks in comparison to all controls (J:135864)
• marked mesangial expansion is observed at 26 weeks of age (J:135864)
• marked mesangial expansion is observed at 26 weeks of age (J:135864)
• marked mesangiolysis is observed at 26 weeks of age (J:135864)
• marked mesangiolysis is observed at 26 weeks of age (J:135864)
• focal nodular sclerosis is observed at 26 weeks of age (J:135864)
• focal nodular sclerosis is observed at 26 weeks of age (J:135864)
• substantial fibronectin accumulation is observed in glomeruli (J:135864)
• substantial fibronectin accumulation is observed in glomeruli (J:135864)
• GFR is decreased in comparison to homozygous Nos3tm1Unc and Leprdb controls (J:135864)
• GFR is decreased in comparison to homozygous Nos3tm1Unc and Leprdb controls (J:135864)

homeostasis/metabolism
• at 26 weeks, serum creatinine is significantly higher than all controls (J:135864)
• at 26 weeks, serum creatinine is significantly higher than all controls (J:135864)
• hyperglycemia is first observed between 6-8 weeks of age, but is not higher than homozygous Leprdb control (J:135864)
• hyperglycemia is first observed between 6-8 weeks of age, but is not higher than homozygous Leprdb control (J:135864)
• albumin/creatinine ratio (ACR) is significantly higher than all controls (J:135864)
• albumin/creatinine ratio (ACR) is significantly higher than all controls (J:135864)

growth/size/body
• at 26 weeks, body weight is double that of lean and Nos3tm1Unc controls (J:135864)
• at 26 weeks, body weight is double that of lean and Nos3tm1Unc controls (J:135864)

cardiovascular system
• arteriolar hyalinosis (J:135864)
• arteriolar hyalinosis (J:135864)
• hypertension is observed between 24-28 weeks of age, but is not significantly higher than homozygous Nos3tm1Unc controls (J:135864)
• hypertension is observed between 24-28 weeks of age, but is not significantly higher than homozygous Nos3tm1Unc controls (J:135864)

Mouse Models of Human Disease
OMIM ID Ref(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:135864




Genotype
MGI:3775795
cx20
Allelic
Composition
Apoetm1Unc/Apoetm1Unc
Leprdb/Leprdb
Genetic
Background
involves: 129P2/OlaHsd * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apoetm1Unc mutation (22 available); any Apoe mutation (64 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• higher levels of "advanced glycation end products" in the extracellular matrix (J:103714)
• Ager mRNA levels elevated in the retina (J:103714)
• higher levels of "advanced glycation end products" in the extracellular matrix (J:103714)
• Ager mRNA levels elevated in the retina (J:103714)
• increase of capillary lesions (J:103714)
• significantly higher number of acellular capillaries (J:103714)
• increased capillary outpouching indicative of early microaneurysms (J:103714)
• increase of capillary lesions (J:103714)
• significantly higher number of acellular capillaries (J:103714)
• increased capillary outpouching indicative of early microaneurysms (J:103714)

cardiovascular system
• increase of capillary lesions (J:103714)
• significantly higher number of acellular capillaries (J:103714)
• increased capillary outpouching indicative of early microaneurysms (J:103714)
• increase of capillary lesions (J:103714)
• significantly higher number of acellular capillaries (J:103714)
• increased capillary outpouching indicative of early microaneurysms (J:103714)




Genotype
MGI:3839678
cx21
Allelic
Composition
Leprdb/Leprdb
Plin1tm1Chan/Plin1tm1Chan
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
Plin1tm1Chan mutation (1 available); any Plin1 mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• mice are resistant to the obesity caused by the Leprdb background (J:66267)
• at a given age, mice weigh significantly less than Leprdb homozygotes but more than wild-type controls (J:66267)
• MRI analysis finds the total lipid signal for these mice at 27% compared to 24% for wild-type and 63% for the Leprdb homozygotes (J:66267)
• mice are resistant to the obesity caused by the Leprdb background (J:66267)
• at a given age, mice weigh significantly less than Leprdb homozygotes but more than wild-type controls (J:66267)
• MRI analysis finds the total lipid signal for these mice at 27% compared to 24% for wild-type and 63% for the Leprdb homozygotes (J:66267)

homeostasis/metabolism
• mice have much higher rates of oxygen consumption compared to controls (J:66267)
• mice have much higher rates of oxygen consumption compared to controls (J:66267)




Genotype
MGI:5548175
cx22
Allelic
Composition
Gdf15tm1Sjl/Gdf15tm1Sjl
Leprdb/Leprdb
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gdf15tm1Sjl mutation (0 available); any Gdf15 mutation (6 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• water intake and urine output are increased at week 9 compared to single Lepr mutants (J:202996)
• water intake and urine output are increased at week 9 compared to single Lepr mutants (J:202996)
• food intake is increased over single Gdf15 mutants but is similar to single Lepr mutants (J:202996)
• food intake is increased over single Gdf15 mutants but is similar to single Lepr mutants (J:202996)

cardiovascular system
• increase in heart weight compared to controls, including that in single Lepr mutants (J:202996)
• increase in heart weight compared to controls, including that in single Lepr mutants (J:202996)

growth/size/body
• body weight is increased over nondiabetic single Gdf15 mutants but is similar to single Lepr mutants (J:202996)
• body weight is increased over nondiabetic single Gdf15 mutants but is similar to single Lepr mutants (J:202996)

homeostasis/metabolism
• increase in serum creatinine levels compared to controls, including that in single Lepr mutants (J:202996)
• increase in serum creatinine levels compared to controls, including that in single Lepr mutants (J:202996)
• nonfasting blood glucose and HbA1c are higher in double mutants than in single Lepr mutants at the final time point of 18 weeks but are similar at earlier time points but higher than in single Gdf15 mutants (J:202996)
• nonfasting blood glucose and HbA1c are higher in double mutants than in single Lepr mutants at the final time point of 18 weeks but are similar at earlier time points but higher than in single Gdf15 mutants (J:202996)
• urinary glucose loss is higher than in single Lepr mutants at week 14 (J:202996)
• urinary glucose loss is higher than in single Lepr mutants at week 14 (J:202996)
• similar increase in cholesterol level as in single Lepr mutants (J:202996)
• similar increase in cholesterol level as in single Lepr mutants (J:202996)
• similar increase in HDL levels as in single Lepr mutants (J:202996)
• similar increase in HDL levels as in single Lepr mutants (J:202996)
• similar increase in urinary albumin excretion as in single Lepr mutants (J:202996)
• similar increase in urinary albumin excretion as in single Lepr mutants (J:202996)

liver/biliary system
• liver weight is increased to a similar extent as in single Lepr mutants (J:202996)
• liver weight is increased to a similar extent as in single Lepr mutants (J:202996)

renal/urinary system
• urinary glucose loss is higher than in single Lepr mutants at week 14 (J:202996)
• urinary glucose loss is higher than in single Lepr mutants at week 14 (J:202996)
• similar increase in urinary albumin excretion as in single Lepr mutants (J:202996)
• similar increase in urinary albumin excretion as in single Lepr mutants (J:202996)
• marker analysis indicates that double mutants show an increase in renal damage and in interstitial and tubular damage in the kidney compared to single Lepr mutants (J:202996)
• marker analysis indicates that double mutants show an increase in renal damage and in interstitial and tubular damage in the kidney compared to single Lepr mutants (J:202996)
• glomerulosclerosis is similar as in single Lepr mutants (J:202996)
• glomerulosclerosis is similar as in single Lepr mutants (J:202996)
• kidney weight is increased to a similar extent as in single Lepr mutants (J:202996)
• kidney weight is increased to a similar extent as in single Lepr mutants (J:202996)
• water intake and urine output are increased at week 9 compared to single Lepr mutants (J:202996)
• water intake and urine output are increased at week 9 compared to single Lepr mutants (J:202996)




Genotype
MGI:3720617
cx23
Allelic
Composition
Aqp9tm1Nlsn/Aqp9tm1Nlsn
Leprdb/Leprdb
Genetic
Background
involves: 129S1/Sv * C57BL/6 * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aqp9tm1Nlsn mutation (1 available); any Aqp9 mutation (4 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• after fasting blood glucose levels are moderately lower than those in Leprdb homozygotes (J:123742)
• after fasting blood glucose levels are moderately lower than those in Leprdb homozygotes (J:123742)
• 939+/-43 compared to 553+/-35 in Leprdb homozygotes (J:123742)
• 939+/-43 compared to 553+/-35 in Leprdb homozygotes (J:123742)




Genotype
MGI:3803207
cx24
Allelic
Composition
Leprdb/Leprdb
Serpine1tm1Mlg/Serpine1tm1Mlg
Genetic
Background
involves: 129S2/SvPas * C57BL/6 * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
Serpine1tm1Mlg mutation (4 available); any Serpine1 mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 23% of females and 44% of males in the F3 generation died prematurely, of indeterminate cause (J:127478)
• 23% of females and 44% of males in the F3 generation died prematurely, of indeterminate cause (J:127478)

growth/size/body
• female mice are obese relative to wild-type and Serpine1-deficient single mutant controls (J:127478)
• female mice are obese relative to wild-type and Serpine1-deficient single mutant controls (J:127478)
• 63% of males in F3 generation are runts with body weight ranging from 20-40 grams compared to 60-100 grams for littermates not displaying runt phenotype (J:127478)
• 63% of males in F3 generation are runts with body weight ranging from 20-40 grams compared to 60-100 grams for littermates not displaying runt phenotype (J:127478)

renal/urinary system
• present with slightly higher urinary albumin to creatinine ratios relative to Lepr single homozygotes (J:127478)
• present with slightly higher urinary albumin to creatinine ratios relative to Lepr single homozygotes (J:127478)
• total kidney collagen is increased in females by 47% compared to female single Serpine1-deficient animals (J:127478)
• total kidney collagen is increased in females by 47% compared to female single Serpine1-deficient animals (J:127478)
• glomerular extracellular matrix (ECM) areas are reduced 10% in females compared to female single Serpine1-deficient animals; however, when expressed as fractional glomerular ECM area, little difference is observed between any genotype (J:127478)
• glomerular extracellular matrix (ECM) areas are reduced 10% in females compared to female single Serpine1-deficient animals; however, when expressed as fractional glomerular ECM area, little difference is observed between any genotype (J:127478)

homeostasis/metabolism
• significantly higher BUN levels compared to Serpine1-deficient single mutants (J:127478)
• significantly higher BUN levels compared to Serpine1-deficient single mutants (J:127478)
• hyperglycemia is less severe than observed in Serpine1-sufficient, Lepr-deficient controls at 10, 14, and 34 weeks of age (J:127478)
• hyperglycemia is less severe than observed in Serpine1-sufficient, Lepr-deficient controls at 10, 14, and 34 weeks of age (J:127478)
• present with slightly higher urinary albumin to creatinine ratios relative to Lepr single homozygotes (J:127478)
• present with slightly higher urinary albumin to creatinine ratios relative to Lepr single homozygotes (J:127478)
• total urokinase plasminogen activator (uPA) activity is significantly higher than wild-type compared to Serpine1-sufficient diabetic controls (J:127478)
• total urokinase plasminogen activator (uPA) activity is significantly higher than wild-type compared to Serpine1-sufficient diabetic controls (J:127478)




Genotype
MGI:5316083
cx25
Allelic
Composition
Leprdb/Leprdb
Rock1tm1Leiw/Rock1tm1Leiw
Genetic
Background
involves: 129S7/SvEvBrd * C57BLKS/J * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
Rock1tm1Leiw mutation (0 available); any Rock1 mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
N
• mice treated with streptozotocin to induce diabetes do not exhibit podocyte loss unlike similarly treated Leprdb homozygotes (J:182287)
• mice treated with streptozotocin to induce diabetes do not exhibit podocyte loss unlike similarly treated Leprdb homozygotes (J:182287)
• mice treated with streptozotocin to induce diabetes exhibit glomerular apoptosis but not as much as in similarly treated Leprdb homozygotes (J:182287)
• mice treated with streptozotocin to induce diabetes exhibit glomerular apoptosis but not as much as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes but not as much as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes but not as much as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes but not as much as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes but not as much as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)

homeostasis/metabolism
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes but not as much as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes but not as much as in similarly treated Leprdb homozygotes (J:182287)

growth/size/body
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)
• in mice treated with streptozotocin to induce diabetes as in similarly treated Leprdb homozygotes (J:182287)

cellular
• mice treated with streptozotocin to induce diabetes exhibit glomerular apoptosis but not as much as in similarly treated Leprdb homozygotes (J:182287)
• mice treated with streptozotocin to induce diabetes exhibit glomerular apoptosis but not as much as in similarly treated Leprdb homozygotes (J:182287)
• mice treated with streptozotocin to induce diabetes exhibit mitochondrial reactive oxygen species production but not as much as in similarly treated Leprdb homozygotes (J:182287)
• mice treated with streptozotocin to induce diabetes exhibit mitochondrial fission but not as much as in similarly treated Leprdb homozygotes (J:182287)
• mice treated with streptozotocin to induce diabetes exhibit mitochondrial reactive oxygen species production but not as much as in similarly treated Leprdb homozygotes (J:182287)
• mice treated with streptozotocin to induce diabetes exhibit mitochondrial fission but not as much as in similarly treated Leprdb homozygotes (J:182287)
• mice treated with streptozotocin to induce diabetes exhibit mitochondrial reactive oxygen species production but not as much as in similarly treated Leprdb homozygotes (J:182287)
• mice treated with streptozotocin to induce diabetes exhibit mitochondrial reactive oxygen species production but not as much as in similarly treated Leprdb homozygotes (J:182287)




Genotype
MGI:5435319
cx26
Allelic
Composition
Leprdb/Lepr+
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: C3H * C57BL/6 * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• nonfasting blood glucose levels are elevated compared to control Leprdb heterozygotes (J:186924)
• however, fasting blood glucose is normal at 5-7 weeks of age (J:186924)
• nonfasting blood glucose levels are elevated compared to control Leprdb heterozygotes (J:186924)
• however, fasting blood glucose is normal at 5-7 weeks of age (J:186924)
• nonfasting and fasting hyperinsulinemia (J:186924)
• nonfasting and fasting hyperinsulinemia (J:186924)
• elevation in nonfasting plasma cholesterol levels (J:186924)
• however, fasting cholesterol levels are normal (J:186924)
• elevation in nonfasting plasma cholesterol levels (J:186924)
• however, fasting cholesterol levels are normal (J:186924)
• mutants exhibit decreased insulin sensitivity (J:186924)
• mutants exhibit decreased insulin sensitivity (J:186924)
• mutants exhibit an increase in expression of amyloid beta protein in plasma compared to Leprdb heterozygotes, however they do not show amyloid beta plaques yet at 5-7 weeks of age (J:186924)
• mutants exhibit an increase in expression of amyloid beta protein in plasma compared to Leprdb heterozygotes, however they do not show amyloid beta plaques yet at 5-7 weeks of age (J:186924)

endocrine/exocrine glands
• increase in beta cell mass and beta cell area compared to control Leprdb heterozygotes (J:186924)
• increase in beta cell mass and beta cell area compared to control Leprdb heterozygotes (J:186924)

growth/size/body
N
• body weight is normal at 5-7 weeks of age (J:186924)
• body weight is normal at 5-7 weeks of age (J:186924)




Genotype
MGI:3693603
cx27
Allelic
Composition
Dbsq1BKS/Dbsq1BKS
Leprdb/Leprdb
Genetic
Background
involves: C3H/HeJ * C57BLKS
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dbsq1BKS mutation (0 available); any Dbsq1 mutation (0 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
adipose tissue
• increased fat pad weight in males (J:116038)
• increased fat pad weight in males (J:116038)




Genotype
MGI:3693604
cx28
Allelic
Composition
Dbsq1BKS/Dbsq1C3H/HeJ
Leprdb/Leprdb
Genetic
Background
involves: C3H/HeJ * C57BLKS
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dbsq1BKS mutation (0 available); any Dbsq1 mutation (0 available)
Dbsq1C3H/HeJ mutation (0 available); any Dbsq1 mutation (0 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
adipose tissue
• increased fat pad weight in males (J:116038)
• increased fat pad weight in males (J:116038)




Genotype
MGI:3693605
cx29
Allelic
Composition
Dbsq2C3H/HeJ/Dbsq2C3H/HeJ
Leprdb/Lepr+
Genetic
Background
involves: C3H/HeJ * C57BLKS
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dbsq2C3H/HeJ mutation (0 available); any Dbsq2 mutation (0 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• increased body weight in males at 7, 8, 9, 10 weeks of age and at sacrifice (J:116038)
• increased body weight in males at 7, 8, 9, 10 weeks of age and at sacrifice (J:116038)




Genotype
MGI:3693606
cx30
Allelic
Composition
Dbsq2BKS/Dbsq2C3H/HeJ
Leprdb/Lepr+
Genetic
Background
involves: C3H/HeJ * C57BLKS
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dbsq2BKS mutation (0 available); any Dbsq2 mutation (0 available)
Dbsq2C3H/HeJ mutation (0 available); any Dbsq2 mutation (0 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• increased body weight in males at 7, 8, 9, 10 weeks of age and at sacrifice (J:116038)
• increased body weight in males at 7, 8, 9, 10 weeks of age and at sacrifice (J:116038)




Genotype
MGI:3693607
cx31
Allelic
Composition
Dbsq3C3H/HeJ/Dbsq3C3H/HeJ
Leprdb/Lepr+
Genetic
Background
involves: C3H/HeJ * C57BLKS
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dbsq3C3H/HeJ mutation (0 available); any Dbsq3 mutation (0 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• increased blood glucose concentration in males at 30, 60, and 120 minutes during the intraperitoneal glucose tolerance test (J:116038)
• increased blood glucose concentration in males at 30, 60, and 120 minutes during the intraperitoneal glucose tolerance test (J:116038)




Genotype
MGI:3693608
cx32
Allelic
Composition
Dbsq3BKS/Dbsq3C3H/HeJ
Leprdb/Lepr+
Genetic
Background
involves: C3H/HeJ * C57BLKS
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dbsq3BKS mutation (0 available); any Dbsq3 mutation (0 available)
Dbsq3C3H/HeJ mutation (0 available); any Dbsq3 mutation (0 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• increased blood glucose concentration in males at 30, 60, and 120 minutes during the intraperitoneal glucose tolerance test (J:116038)
• increased blood glucose concentration in males at 30, 60, and 120 minutes during the intraperitoneal glucose tolerance test (J:116038)




Genotype
MGI:5552736
cx33
Allelic
Composition
Ccr2tm1.1(CCR2)Rodb/Ccr2tm1.1(CCR2)Rodb
Leprdb/Leprdb
Genetic
Background
involves: C57BL/6 * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccr2tm1.1(CCR2)Rodb mutation (0 available); any Ccr2 mutation (6 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• CCX140-B treatment improves albuminuria (J:203000)
• CCX140-B treatment improves albuminuria (J:203000)

renal/urinary system
• CCX140-B treatment improves albuminuria (J:203000)
• CCX140-B treatment improves albuminuria (J:203000)




Genotype
MGI:5427610
cx34
Allelic
Composition
Leprdb/Leprdb
Tg(Fabp4-Fcor)1Jnak/0
Genetic
Background
involves: C57BL/6 * C57BLKS/J * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (11 available); any Lepr mutation (37 available)
Tg(Fabp4-Fcor)1Jnak mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• compared with Leprdb homozygotes (J:184684)
• compared with Leprdb homozygotes (J:184684)
• compared with Leprdb homozygotes (J:184684)
• compared with Leprdb homozygotes (J:184684)
• compared with Leprdb homozygotes (J:184684)
• compared with Leprdb homozygotes (J:184684)

adipose tissue
• decreased visceral fat compared with Leprdb homozygotes (J:184684)
• however, subcutaneous and total adipose mass are normal (J:184684)
• decreased visceral fat compared with Leprdb homozygotes (J:184684)
• however, subcutaneous and total adipose mass are normal (J:184684)
• compared with Leprdb homozygotes (J:184684)
• compared with Leprdb homozygotes (J:184684)

growth/size/body
• compared with Leprdb homozygotes (J:184684)
• compared with Leprdb homozygotes (J:184684)




Genotype
MGI:3529778
cx35
Allelic
Composition
Cdkn1btm1Kin/Cdkn1b+
Leprdb/Leprdb
Genetic
Background
involves: C57BL/6J * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1btm1Kin mutation (1 available); any Cdkn1b mutation (13 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological

endocrine/exocrine glands
• islet mass, but not islet density, is significantly increased compared to Lepr single homozygotes (J:96047)
• islet mass, but not islet density, is significantly increased compared to Lepr single homozygotes (J:96047)
• beta cell proliferation and the total number of beta cells are increased compared to Lepr single homozygotes; however the size of individual beta cells is similar to Lepr single homozygotes (J:96047)
• beta cell proliferation and the total number of beta cells are increased compared to Lepr single homozygotes; however the size of individual beta cells is similar to Lepr single homozygotes (J:96047)

growth/size/body

homeostasis/metabolism
• developed more slowly and to a reduced extent compared to Lepr single homozygotes (J:96047)
• developed more slowly and to a reduced extent compared to Lepr single homozygotes (J:96047)




Genotype
MGI:3529774
cx36
Allelic
Composition
Cdkn1btm1Kin/Cdkn1btm1Kin
Leprdb/Leprdb
Genetic
Background
involves: C57BL/6J * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1btm1Kin mutation (1 available); any Cdkn1b mutation (13 available)
Leprdb mutation (11 available); any Lepr mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological

endocrine/exocrine glands
• islet mass, but not islet density, is significantly increased compared to Lepr single homozygotes (J:96047)
• islet mass, but not islet density, is significantly increased compared to Lepr single homozygotes (J:96047)
• beta cell proliferation and the total number of beta cells are increased compared to Lepr single homozygotes; however the size of individual beta cells is similar to Lepr single homozygotes (J:96047)
• beta cell proliferation and the total number of beta cells are increased compared to Lepr single homozygotes; however the size of individual beta cells is similar to Lepr single homozygotes (J:96047)

growth/size/body

homeostasis/metabolism
• hyperlipidemia similar to Lepr single homozygotes is seen; however, double homozygotes do not develop hyperglycemia (J:96047)
• hyperlipidemia similar to Lepr single homozygotes is seen; however, double homozygotes do not develop hyperglycemia (J:96047)





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last database update
02/02/2016
MGI 6.02
The Jackson Laboratory