Phenotypes Associated with This Genotype

Genotype
MGI:3655832

• Allelic Composition: Lepr^db/Lepr^db
• Genetic Background: FVB.BKS-Lepr^db

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

growth/size/body

obese ( J:78850 )

• mice of both sexes are obese

homeostasis/metabolism

abnormal circulating glucose level ( J:78850 )

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

hyperglycemia ( J:78850 )

• Background Sensitivity: obese mice have a prolonged period of hyperglycemia compared to obese B6.BKS-Lepr^db mice where glucose levels rarely exceed 250 mg/dl

• fasting mice are hyperglycemic at 3 months of age, while obese B6.BKS-Lepr^db fasted mice are euglycemic

• levels increase from 5 to 7 months in obese females to ~500 ng/ml, significantly higher than the males (~40 ng/ml) or obese B6.BKS-Lepr^db females (~50 ng/ml)

increased circulating insulin level ( J:78850 )

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

impaired glucose tolerance ( 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-Lepr^db mice clear glucose load by 90 min

• Background Sensitivity: obese mice show a rapid increase of blood glucose above 400 mg/dl with diminished rate of glucose clearance

insulin resistance ( J:78850 )

• at 7 months of age, 3U/kg of insulin does not alter circulating glucose levels, while in B6.BKS-Lepr mice, glucose decreases by 50% by 40 minutes; 12U/kg insulin does not cause a decrease in glucose in obese female mice on the FVB background

• at a dose of 3U/kg 6-week old mice show a diminished response to insulin

• circulating insulin levels in the fed state show that obese mice have exteme insulin resistance

endocrine/exocrine glands

increased pancreatic beta cell number ( J:78850 )

• obese mice show massive expansion of beta cells (744 insulin +ve cells/islet cross-section in obese vs 165 +ve cells in lean mice); there are 4.5-fold more cells per islet cross-section in obese mice

pancreatic islet hyperplasia ( J:78850 )

• some islets in obese mice have more than 1000 cells per cross section; such islets are absent in lean mice

renal/urinary system

abnormal renal glomerulus morphology ( J:78850 )

• at 7 months of age, obese mice show an increased mesangial matrix in most glomeruli compared to lean controls, resembling diabetic nephropathy; some small glomeruli have separated from the capsule with nearly obliterated microtubules

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:78850