Assessment of diabetic nephropathy in the Akita mouse.
Akita mice have type 1 diabetes mellitus caused by a spontaneous point mutation in the Ins2 gene which leads to misfolding of insulin, resulting in pancreatic β-cell failure. Akita mice develop pronounced and sustained hyperglycemia, high levels of albuminuria, and consistent histopathological changes, suggesting that these mice may be suitable as an experimental platform for modeling diabetic nephropathy. One key feature of diabetic kidney disease in Akita mice is that the severity of renal injury is significantly influenced by genetic background. In this chapter, we describe the Akita model and present some of the experimental studies utilizing Akita mice as a model of type 1 diabetes. For example, deficiency in bradykinin receptors, endothelial nitric oxide synthase, or angiotensin-converting enzyme 2 leads to development of functionally and structurally more advanced diabetic nephropathy in these mice, while ketogenic diet has been shown to reverse kidney injury associated with diabetes. This chapter also describes the application of 24-h urine collections from mice for careful measurement of urinary albumin excretion.
Division of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, Durham, NC, USA.
Jae-Hyung
JH
Chang
Susan B
SB
Gurley
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D007328:Insulin / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017354:Point Mutation; D016482:Urinalysis / Q000379:methods
C561967:Ins2 protein, mouse; D007328:Insulin; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2