An Animal Model of Kidney Disease Associated with Mitochondrial Dysfunction Made by Collecting Duct-Specific Deletion of CR6-Interacting Factor 1
DE Choi, JY Jeong, KR Na, KW Lee, YT Shin, HJ Jeong, BJ Lim. Chungnam National University College of Medicine, Daejeon, Korea; Yonsei University College of Medicine, Seoul, Korea
Background: The importance of mitochondria in kidney disease has been recently discovered and an appropriate animal model of mitochondria-associated kidney disease has not been developed yet. CR6-interacting factor 1 (Crif1) is a recently found intranuclear protein which plays an important role in the assembly and stabilization of mitochondria. In this study, we aimed to develop an animal model having mitochondrial dysfunction limited to the kidney by cell-specific gene knock out technique.
Design: To induce collecting duct-specific Crif1 knock out, we used Cre-loxP system. Cre mice having HoxB7 as a collecting duct-specific promotor were mated with Crif1-floxed mice. Among the second generation offsprings, we selected Crif1 homozygously deleted mice and performed the evaluation of physiologic parameters, light microscopic examinations, immunohistochemical stainings for Crif1 and various receptors, and electron microscopic examiniations.
Results: The histologic alteration was not remarkable on light microscopic examinations. However, electron microscopy revealed marked alteration of mitochondria such as size variabilitity, abnormal cristae formation, degeneration and autophagy formation. These features were observed exclusively in collecting duct epithelial cells. The urine volue was decreased and the serum creatinin level was slightly increased.
Conclusions: We developed a collecting duct-specific mitochondrial dysfunction model using Cre-loxP system in mice. This model can be expanded to other mitochondrial disease of the kidney by using another cell-specific promotors (for example, podocin for podocyte).
Category: Kidney (does not include tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 250, Wednesday Afternoon