The KKA ^y Mouse: A Model for the Rapid Development of Glomerular Capillary Basement Membrane Thickening

Abstract

The renal tissue of 12-, 29-, 90- and 165-day-old genetically obese, hyperphagic, diabetic KKA^y and age-matched nondiabetic C57BL/6 mice was morphometrically analyzed to characterize the development of peripheral glomerular capillary basement membrane thickening in the kidney of this animal model. Peripheral glomerular basement membrane (GBM) thickness was unremarkable in KKA^y mice at 12 days of age (prior to onset of hyperinsulinemia) or at 29 days of age (after development of hyperinsulinemia). By 90 days of age, when the KKA^y mice became severely hyperinsulinemic and hyperglycemic, the peripheral GBM thickness was greater (13%, p < 0.002) in the diabetic compared with the nondiabetic mice. Furthermore, the peripheral GBM thickness was exacerbated (20%, p < 0.001) by 165 days of age in the KKA^y mice. The results of the present study suggest that peripheral glomerular capillary basement membrane thickening has an early onset and develops rapidly in the KKA^y mouse in comparison with other diabetic animal models. Therefore, the KKA^y mouse seems to be an appropriate model for further investigation of early structural and functional defects in the glomerular filtration barrier.