Mouse Genome Informatics
hm
    Lepob/Lepob
BTBR.Cg-Lepob/WiscJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
cardiovascular system
N
• mice do not develop atherosclerosis (J:185261)

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

homeostasis/metabolism
• increased BUN levels in both male and female mice
• 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)
• mice are hyperinsulinemic by 6 weeks of age but levels decrease as glucose levels rise
• increased serum triglyceride levels in both male and female mice (J:185261)
• inability to clear plasma glucose following an overnight fast
• 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 levels in both male and female mice
• 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
• 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
• reduced podocyte density
• reduced podocyte number
• glomerular basement membrane thickness is increased by 18% as compared to wild-type
• renal lesions are characterized by increased glomerular mesangial matrix accumulation
• 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
• increased glomerular size
• 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
• renal hypertrophy
• both sexes exhibit increased kidney weight as compared to wild-type
• kidney weight of males is increased compared to females

endocrine/exocrine glands
• 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
• many small islets that show poor insulin staining

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:106121