Phenotypes Associated with This Genotype

Genotype
MGI:5428893

• Allelic Composition: Lep^ob/Lep^ob
• Genetic Background: BTBR.Cg-Lep^ob/WiscJ

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

cardiovascular system

cardiovascular system phenotype ( J:185261 )

N • mice do not develop atherosclerosis

hypotension ( J:185261 )

growth/size/body

increased body weight ( J:185261 )

• body weight is increased by 8 weeks of age as compared to heterozygotes and wild-type

enlarged kidney ( J:185261 )

• renal hypertrophy

increased kidney weight ( J:185261 )

• both sexes exhibit increased kidney weight as compared to wild-type

• kidney weight of males is increased compared to females

homeostasis/metabolism

increased blood urea nitrogen level ( J:185261 )

• increased BUN levels in both male and female mice

hyperglycemia ( J:106121 , J:185261 )

• hyperglycemia is more evident in males than females, but after a time delay, also occurs in females (J:106121)

• mice exhibit hyperglycemia by 8 weeks of age (J:185261)

• males progress to blood glucose levels of 399 +/- 38.8 mg/dl by 22 weeks of age (J:185261)

• females progress to blood glucose levels of 333 +/- 46.3 mg/dl by 22 weeks of age (J:185261)

• Background Sensitivity: blood glucose levels are higher than obese mice on the C57BL/6 background (J:185261)

increased circulating insulin level ( J:106121 )

• mice are hyperinsulinemic by 6 weeks of age but levels decrease as glucose levels rise

increased circulating triglyceride level ( J:106121 , J:185261 )

• increased serum triglyceride levels in both male and female mice (J:185261)

impaired glucose tolerance ( J:106121 )

• inability to clear plasma glucose following an overnight fast

insulin resistance ( J:106121 )

• at 6 weeks of age, most females are insulin resistant; they are hyperinsulinemic while maintaining only moderately elevated glucose levels

• by 10 weeks of age, female mice are hyperglycemic while still maintaining high (but insufficient) levels of insulin

• by 14 weeks of age, many females have even lower plasma insulin and increasing plasma glucose levels

• males show a similar progression of insulin resistance as females but starting at an earlier age, showing high insulin and high glucose at 6 weeks of age

increased cholesterol level ( J:185261 )

• increased cholesterol levels in both male and female mice

albuminuria ( J:185261 )

• albuminuria is detected as early as 8 weeks of age, progressing to a 10-fold difference by 20 weeks of age

• increased albumin creatinine ratio

renal/urinary system

enlarged kidney ( J:185261 )

• renal hypertrophy

increased kidney weight ( J:185261 )

• both sexes exhibit increased kidney weight as compared to wild-type

• kidney weight of males is increased compared to females

albuminuria ( J:185261 )

• albuminuria is detected as early as 8 weeks of age, progressing to a 10-fold difference by 20 weeks of age

• increased albumin creatinine ratio

abnormal podocyte morphology ( J:185261 )

• reduced podocyte density

• reduced podocyte number

increased renal glomerulus basement membrane thickness ( J:185261 )

• glomerular basement membrane thickness is increased by 18% as compared to wild-type

expanded mesangial matrix ( J:185261 )

• renal lesions are characterized by increased glomerular mesangial matrix accumulation

mesangiolysis ( J:185261 )

• mesangiolysis is observed in 8% of glomeruli 8 week old mice

• mesangiolysis increases with age reaching 33.1% by 22 weeks of age

• diffuse mesangial sclerosis

glomerulosclerosis ( J:185261 )

renal glomerulus hypertrophy ( J:185261 )

• increased glomerular size

renal interstitial fibrosis ( J:185261 )

• focal and mild interstitial fibrosis is observed in 12 week old mice

• interstitial collagen accumulation is increased at 24 weeks of age as compared to wild-type

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:106121 )

• architecture of islets is disrupted, with many noninsulin staining cells in the central core

• whole pancreas insulin content is reduced by 75-80% compared to mutants on the C57BL/6 background

decreased pancreatic beta cell mass ( J:106121 )

small pancreatic islets ( J:106121 )

• many small islets that show poor insulin staining

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:106121