Date of Award

2012

Document Type

Thesis

Department

Chemistry

First Advisor

Dr. Joe Jeffers

Second Advisor

Dr. Marty Perry

Third Advisor

Dr. Randall Wight

Abstract

Podocytes are vital, specialized kidney cells that are post-mitotic and cannot proliferate. Nevertheless, regeneration of podocytes after low-level ablation from a presently unidentified stem cell pool has been observed. The objective of this study was to establish a mouse model for the study of this regeneration process. Two transgenic mice were developed, the first of which possessed a tomato-reporter transgene for the assessment of podocyte turnover. Adriamycin was used to induce podocyte damage in this mouse. The second transgenic mouse possessed the tomato-reporter transgene as well as transgene allowing for the diphtheria toxin inducible (iDTR) ablation of podocytes. Dosage tests were conducted to evaluate the effectiveness of these models in ablating podocytes. Both the Adrimycin and tDTR mouse models successfully induced podocyte damage, with the iDTR system being ~1500x more effective. The models exhibited podocyte damage far exceeding the threshold at which regeneration becomes impossible. Lower-level ablation is needed, and further iDTR dosage tests will be conducted to determine the optimal drug dosages.

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