Hereditary diabetes in the KK mouse: an overview

Area of Science:

• Endocrinology
• Genetics
• Nephrology

Background:

• KK mice exhibit metabolic and morphologic differences compared to control strains.
• Swiss albino mice show glucose intolerance, hyperinsulinism, and obesity, suggesting a genetic predisposition.
• The yellow AY mouse is hyperinsulinemic and obese but lacks vasculopathy.

Purpose of the Study:

• To compare metabolic and morphologic characteristics of KK mice with control strains.
• To investigate the development of diabetes and microangiopathy in KK mice.
• To establish KK mice as a model for non-insulin-dependent diabetes mellitus.

Main Methods:

• Comparative analysis of metabolic and morphologic data from various mouse strains.
• Histologic examination for glomerular lesions and other abnormalities.
• Genetic back-crossing studies to assess heritability of hyperglycemia and glomerulosclerosis.

Main Results:

• KK mice develop chemical diabetes, prediabetes, and complications affecting renal, retinal, and neurologic systems.
• Glomerulosclerosis progresses from mild/moderate in the prediabetic stage to severe with proteinuria later.
• Hyperglycemia and glomerulosclerosis are transmissible to normal mice via back-crossing, indicating a genetic basis.

Conclusions:

• KK mice serve as an ideal genetic model for studying non-insulin-dependent diabetes mellitus and its complications.
• A specific genetic background is necessary for the development of diabetes and diabetic-like microangiopathy.
• Findings support the use of KK mice for research into prevention and therapy of diabetes and its sequelae.