Phenotypes Associated with This Genotype

Genotype
MGI:3689720

• Allelic Composition: Lepr^db/Lepr^db
• Genetic Background: B6.Cg-Dock7^m +/+ Lepr^db/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

growth/size/body

heart left ventricle hypertrophy ( J:103063 )

• increase in left ventricle wall thickness and mass is seen by 6 months of age but not at 2 months of age

• induced weight loss via leptin infusion, but not via caloric restriction, partially resolves the hypertrophy

obese ( J:18161 , J:82334 , J:103063 )

• 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 Leprr^tm1Mgmj homozygotes (J:82334)

• develop progressive obesity (J:103063)

decreased body length ( J:82334 )

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

behavior/neurological

polyphagia ( J:82334 )

reduced male mating frequency ( J:6157 )

♂

cardiovascular system

abnormal myocardial fiber morphology ( J:103063 )

• exhibit myocyte hypertrophy

heart left ventricle hypertrophy ( J:103063 )

• increase in left ventricle wall thickness and mass is seen by 6 months of age but not at 2 months of age

• induced weight loss via leptin infusion, but not via caloric restriction, partially resolves the hypertrophy

muscle

abnormal myocardial fiber morphology ( J:103063 )

• exhibit myocyte hypertrophy

heart left ventricle hypertrophy ( J:103063 )

• increase in left ventricle wall thickness and mass is seen by 6 months of age but not at 2 months of age

• induced weight loss via leptin infusion, but not via caloric restriction, partially resolves the hypertrophy

homeostasis/metabolism

abnormal circulating lipid level ( J:18161 )

• HDL cholesterol and glucose levels increase concurrently

• Background Sensitivity: plasma lipid levels are similar at 3.5 and 14 months of age on the C57BL/6J background unlike on a C57BL/KsJ background

abnormal circulating cholesterol level ( J:18161 )

increased circulating cholesterol level ( J:18161 )

• fasting plasma total cholesterol concentration is increased 2 fold over controls

increased circulating HDL cholesterol level ( J:18161 )

increased circulating LDL cholesterol level ( J:18161 )

increased circulating VLDL cholesterol level ( J:18161 )

increased circulating triglyceride level ( J:18161 , J:82334 )

• triglyceride levels are elevated 1.5- to 2-fold (J:18161)

abnormal glucose homeostasis ( J:82334 )

increased circulating glucose level ( J:82334 )

hyperglycemia ( J:18161 )

abnormal hormone level ( J:6157 )

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

increased circulating insulin level ( J:82334 )

increased circulating leptin level ( J:82334 , J:115772 )

decreased circulating adiponectin level ( J:115772 )

• decreased adiponectin levels in serum

abnormal chemokine level ( J:115772 )

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

abnormal interleukin level ( J:115772 )

• elevated levels of IL-6 in bronchoalveolar lavage fluid

increased circulating interleukin-6 level ( J:115772 )

• elevated levels of IL-6 in serum

reproductive system

abnormal female reproductive system morphology ( J:82334 )

♀ • atrophy of the reproductive organs

small uterus ( J:6157 )

♀

constricted vagina orifice ( J:6157 )

♀

anovulation ( J:82334 )

♀

absent estrus ( J:82334 )

♀ • females never show signs of vaginal oestrous

absent estrous cycle ( J:6157 )

♀ • mice exhibit diestrous vaginal acyclicity or occasional metestrous acyclicity

female infertility ( J:6157 , J:82334 )

♀ (J:6157)

♀ • all females fail to reproduce (J:82334)

respiratory system

lung inflammation ( J:115772 )

• elevated levels of eotaxin, Il6, keratinocyte cytokine, monocyte chemotactic protein-1, and neutrophiles in bronchoalveolar lavage as a result of ozone exposure

• ozone induces significantly elevated levels of TNFR1

• ozone induces a nonsignificant elevation of TNFR2 levels

• elevated pulmonary levels of Il1beta mRNA 24 hours after ozone exposure

• elevated pulmonary levels of TNF mRNA 24 hours after ozone exposure but to a lesser extent than in controls

abnormal functional residual capacity ( J:115772 )

• reduced

• pressure volume curves shifted to the right

abnormal respiratory mechanics ( J:115772 )

• end-expiratory pause increases considerably less than in controls after ozone exposure

abnormal lung compliance ( J:115772 )

• total lung resistance increases much more in response to ozone than in control mice

• responsiveness to methacholine and serotonin is much greater than controls

decreased pulmonary ventilation ( J:115772 )

• ventilation volumes decline with ozone exposure but to a lesser degree than for controls

immune system

abnormal leukocyte morphology ( J:115772 )

increased neutrophil cell number ( J:115772 )

• increased numbers in bronchoalveolar lavage

decreased leukocyte cell number ( J:115772 )

• decrease blood leukocyte numbers

abnormal chemokine level ( J:115772 )

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

abnormal interleukin level ( J:115772 )

• elevated levels of IL-6 in bronchoalveolar lavage fluid

increased circulating interleukin-6 level ( J:115772 )

• elevated levels of IL-6 in serum

lung inflammation ( J:115772 )

• elevated levels of eotaxin, Il6, keratinocyte cytokine, monocyte chemotactic protein-1, and neutrophiles in bronchoalveolar lavage as a result of ozone exposure

• ozone induces significantly elevated levels of TNFR1

• ozone induces a nonsignificant elevation of TNFR2 levels

• elevated pulmonary levels of Il1beta mRNA 24 hours after ozone exposure

• elevated pulmonary levels of TNF mRNA 24 hours after ozone exposure but to a lesser extent than in controls

neoplasm

increased metastatic potential ( J:117826 )

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

hematopoietic system

abnormal leukocyte morphology ( J:115772 )

increased neutrophil cell number ( J:115772 )

• increased numbers in bronchoalveolar lavage

decreased leukocyte cell number ( J:115772 )

• decrease blood leukocyte numbers

nervous system

abnormal hypothalamus physiology ( J:6157 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:18161 , J:82234 , J:103063