Phenotypes Associated with This Genotype

Genotype
MGI:4361710

• Allelic Composition: Lepr^db/Lepr^db; Nos3^tm1Unc/Nos3^tm1Unc
• Genetic Background: BKS.Cg-Lepr^db Nos3^tm1Unc

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

renal/urinary system

albuminuria ( J:135864 )

• albumin/creatinine ratio (ACR) is significantly higher than all controls

abnormal nephron morphology ( J:135864 )

abnormal kidney afferent arteriole morphology ( J:135864 )

• arteriolar hyalinosis

increased renal glomerulus basement membrane thickness ( J:135864 )

• glomerular basement membrane is markedly thickened by 16 weeks in comparison to all controls

abnormal renal glomerulus morphology ( J:135864 )

• glomerular injury is significantly increased by 24-26 weeks in comparison to all controls

expanded mesangial matrix ( J:135864 )

• marked mesangial expansion is observed at 26 weeks of age

mesangiolysis ( J:135864 )

• marked mesangiolysis is observed at 26 weeks of age

glomerulosclerosis ( J:135864 )

• focal nodular sclerosis is observed at 26 weeks of age

renal glomerulus fibrosis ( J:135864 )

• substantial fibronectin accumulation is observed in glomeruli

decreased renal glomerular filtration rate ( J:135864 )

• GFR is decreased in comparison to homozygous Nos3^tm1Unc and Lepr^db controls

homeostasis/metabolism

increased circulating creatinine level ( J:135864 )

• at 26 weeks, serum creatinine is significantly higher than all controls

hyperglycemia ( J:135864 )

• hyperglycemia is first observed between 6-8 weeks of age, but is not higher than homozygous Lepr^db control

albuminuria ( J:135864 )

• albumin/creatinine ratio (ACR) is significantly higher than all controls

growth/size/body

increased body weight ( J:135864 )

• at 26 weeks, body weight is double that of lean and Nos3^tm1Unc controls

cardiovascular system

abnormal kidney afferent arteriole morphology ( J:135864 )

• arteriolar hyalinosis

increased systemic arterial systolic blood pressure ( J:135864 )

• hypertension is observed between 24-28 weeks of age, but is not significantly higher than homozygous Nos3^tm1Unc controls

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:135864