Phenotypes associated with this allele

• Allele Symbol: Lepr^db-3J
• Allele Name: diabetes 3 Jackson
• Allele ID: MGI:1856012
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lepr^db-3J/Lepr^db-3J	129P3/J-Lepr^db-3J/J	MGI:3586756
hm2	Lepr^db-3J/Lepr^db-3J	B6.129-Lepr^db-3J	MGI:3655833

Genotype
MGI:3586756

hm1

• Allelic Composition: Lepr^db-3J/Lepr^db-3J
• Genetic Background: 129P3/J-Lepr^db-3J/J

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

Lepr^db-3J/Lepr^db-3J

mortality/aging

premature death ( J:6337 )

• reduced lifespan, with 67% mortality between 6 and 14 months of age

growth/size/body

weight loss ( J:6337 )

• older mice exhibit sudden weight loss before death

increased body weight ( J:6337 )

obese ( J:6337 )

• homozygotes accumulated excessive fat by 3 weeks of age

• by 6 months of age, mice weighed from 70-90 grams compared to 20-28 grams in controls

behavior/neurological

polyphagia ( J:6337 )

endocrine/exocrine glands

abnormal exocrine pancreas morphology ( J:6337 )

• necrosis of the exocrine, but not the endocrine pancreas was noted in aging animals

increased pancreatic alpha cell number ( J:6337 )

• less than 2-fold increase in the number of alpha cells per islet

increased pancreatic beta cell number ( J:6337 )

• beta cell hyperplasia

pancreatic islet hyperplasia ( J:6337 )

homeostasis/metabolism

hypoglycemia ( J:6337 )

• aged mice become hypoglycemic by 9 months of age

hyperglycemia ( J:6337 )

♂ • mutant males, but not females, were transiently hyperglycemic between 2 and 4 months of age

♂ • glucose levels declined thereafter

increased circulating glucagon level ( J:6337 )

• plasma glucagon levels were increased by 3-fold in young mice and 5-fold in aged mice

• pancreatic glucagon content was only doubled compared to controls at 8 months of age

increased circulating insulin level ( J:6337 )

• at 5 months of age, plasma insulin levels were 30-fold greater in males, and 18-fold greater in females than in controls

• pancreatic insulin levels were 30-fold greater than controls at 8 months of age

reproductive system

infertility ( J:6337 )

• mice are sterile

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:6337 )

• necrosis of the exocrine, but not the endocrine pancreas was noted in aging animals

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:6337

Genotype
MGI:3655833

hm2

• Allelic Composition: Lepr^db-3J/Lepr^db-3J
• Genetic Background: B6.129-Lepr^db-3J

homeostasis/metabolism

abnormal glucose homeostasis ( J:78850 )

• Background Sensitivity: fasting mice at 3 months of age are euglycemic compaired to hyperglycemic obese mice on a congenic FVB background at 3 months

• Background Sensitivity: mice clear glucose load by 90 minutes, while on the FVB background, obese mice have severely impaired glucose tolerance

abnormal circulating glucose level ( J:78850 )

• Background Sensitivity: after a 2-day fast on refeeding with carbohydrate-free diet, female obese mice do not show a rise in glucose, while on the FVB background glucose levels increase

abnormal circulating insulin level ( J:78850 )

• Background Sensitivity: at 3 months, female obese mice have slightly lower insulin levels than FVB.BKS-Lepr^db females; levels increase to ~50 ng/ml at 5-7 months compared to ~500 ng/ml for obese FVB.BKS-Lepr^db females

increased insulin sensitivity ( J:78850 )

• in response to 3U/kg insulin, blood glucose drops 50% in 40 minutes while no change is seen in mice on the FVB background