MICROMouse Program Application Abstract
Characterization of a New Murine Model of Reversal of Diabetic Nephropathy
Charles Alpers (Seattle, WA)
We have preliminary data indicating a new model of diabetic nephropathy, the BTBRob/ob mouse strain with the ob/ob leptin deficiency and Type II diabetes, develops rapid onset of nephropathy, and a glomerulopathy more closely resembling human DN than other widely used murine models, including loss of podocytes. We present preliminary data that reversal of diabetes with leptin restoration can reverse the lesions of DN and may restore normal podocyte number, the first evidence that this can be achieved in a model of DN. We will employ leptin replacement to better establish the model. We will examine whether glomerular podocyte number is reduced as a result of increased apoptosis or detachment in the evolution of diabetic nephropathy, and test the corollary hypothesis that reestablishment of normal podocyte number consequent to cessation of these processes is required for reversal of DN. We will employ the UW MMPC to measure numerous functional and structural parameters of DN, and to develop and perform rigorous measures of podocyte number enabling us to test whether this parameter is essential or not for the development and/or regression of DN.
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