L TIAN1, D NIKOLIC-PATERSON1,2, G TESCH1,2
1Monash Health, Clayton, Australia, 2Monash University Centre for Inflammatory Diseases, Clayton, Australia
Aim: To compare diabetic renal injury in male and female Nos3 deficient mice with equivalent diabetes.
Background: Streptozotocin (STZ)-induced diabetic nephropathy in male mice lacking endothelial nitric oxide synthase (Nos3-/-) is a widely used model for examining the development of diabetic nephropathy. In some mouse strains, females are partially protected from STZ-diabetes and are not used for studies of diabetic nephropathy. In this study, we sought to identify whether male and female Nos3-/- mice with equivalent diabetes develop similar renal injury, justifying the potential to use both sexes in studies of diabetic nephropathy.
Methods: Male and female Nos3-/- mice were made diabetic with multiple low-dose streptozotocin (STZ) injections. Groups of male and female mice with equivalent diabetes at week 2 after STZ were assessed for diabetic kidney injury (albuminuria, renal function impairment, glomerulosclerosis, tubular injury) at week 8.
Results: STZ-treated male and female Nos3-/- mice maintained similar blood glucose levels between weeks 2 and 8 and had equivalent HbA1c levels at week 8 (11.9±0.8% males vs 11.9±0.9% females). At week 8, urine albumin/creatinine levels were elevated 8-fold in both diabetic males and females. Plasma cystatin-C levels increased by 32% in diabetic males (441±64ng/mL) and 35% in diabetic females (463±38ng/mL). The glomerular area of collagen IV immunostaining increased by approximately 30% in both diabetic males and females. In addition, kidney expression of KIM-1 increased by 23±7 fold in males and 26±6 fold in females, indicating similar diabetic tubular injury.
Conclusion: Our study shows that male and female Nos3-/- mice develop equivalent diabetic kidney injury, demonstrating it is possible to include males and females together in studies of diabetic nephropathy.
Lifang Tian is a visiting Chinese research fellow working in the Nephrology Department at Monash Health