Phenotypes Associated with This Genotype

Genotype
MGI:3760281

• Allelic Composition: A^y/a
• Genetic Background: involves: KK

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

homeostasis/metabolism

hyperglycemia ( J:26460 )

• blood glucose levels increase with age in both sexes

• marked hyperglycemia (400-500 mg/dl) develops by 16 weeks of age

increased circulating insulin level ( J:26460 )

• markedly elevated plasma immunoreactive insulin (IRI) level increases with age

impaired glucose tolerance ( J:26460 )

increased urine glucose level ( J:26460 )

• present at all ages tested (5, 10, 16 weeks) and in both sexes

insulin resistance ( J:26460 )

• insulin sensitivity is impaired at 10 weeks and lost by 16 weeks

abnormal lipid homeostasis ( J:26460 )

• lipogenesis from acetate is elevated at 5 weeks of age, the enhanced activity is maintained until 16 weeks of age

• the acetate/glucose ratio is higher than control in young mice

adipose tissue

increased total body fat amount ( J:26460 )

• adipose tissue weight increases with age, reaching a maximum at 10 weeks of age

growth/size/body

increased susceptibility to weight gain ( J:26460 )

• greater body weight gain occurs in females as compared to black KK controls

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:26460 )

• islets are hypertrophic in 10-16 week old mice

• central cavity formation with occasional red blood cells is observed in islets

degranulated pancreatic beta cells ( J:26460 )

• beta cells are degranulated

• degranulated islets are infiltrated with fine glycogen granules

renal/urinary system

increased urine glucose level ( J:26460 )

• present at all ages tested (5, 10, 16 weeks) and in both sexes

increased renal glomerulus basement membrane thickness ( J:26460 )

• basement membrane of Bowman's capsules is thickened

abnormal renal glomerulus morphology ( J:26460 )

• some glomeruli exhibit an accumulation of eosinophilic material in the outer parts of the capillary

expanded mesangial matrix ( J:26460 )

• mesangial matrix is thickened

abnormal renal tubule morphology ( J:26460 )

• basement membrane of tubules is thickened

• hyaline materials or hyaline cast is present in tubules

dilated renal tubule ( J:26460 )

renal cast ( J:26460 )

• hyaline materials or hyaline cast is present in tubules

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:26460