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Investigating mechanisms of chronic kidney disease in mouse models

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Abstract

Animal models of chronic kidney disease (CKD) are important experimental tools that are used to investigate novel mechanistic pathways and to validate potential new therapeutic interventions prior to pre-clinical testing in humans. Over the past several years, mouse CKD models have been extensively used for these purposes. Despite significant limitations, the model of unilateral ureteral obstruction (UUO) has essentially become the high-throughput in vivo model, as it recapitulates the fundamental pathogenetic mechanisms that typify all forms of CKD in a relatively short time span. In addition, several alternative mouse models are available that can be used to validate new mechanistic paradigms and/or novel therapies. Here, we review several models—both genetic and experimentally induced—that provide investigators with an opportunity to include renal functional study end-points together with quantitative measures of fibrosis severity, something that is not possible with the UUO model.

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Acknowledgments

The authors would like to acknowledge the research grants that have supported some of their own work that was cited: National Institutes of Health RO1DK54500 and P50DK44757 (AAE), K08DK073497 and RO3DK083648 (DO), K08DK080926 (IY), R03DK58925 (J L-G), the National Kidney Foundation Young Investigator Award (DO), the American Society of Nephrology Young Investigator Award (IY), Seattle Children’s Research Institute and the Robert O. Hickman Endowed Chair in Pediatric Nephrology. Several people contributed to our own studies that were cited in this review, including two talented research technicians (Xiaohe Cia and Sarah Collins) and several research fellows/visiting scientists (Drs. Takashi Oda, Heungsoo Kim, Guoqiang Zhang, Shunya Matsuo, and Masateru Yamada). We would like to acknowledge Dr. Shelia Violette and Dr. Kent Doi who provided high-resolution digital photomicrographs.

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Authors and Affiliations

  1. Center for Tissue and Cell Sciences, Seattle Children’s Research Institute, 1900 Ninth Avenue, M/S C9S-5, Seattle, WA, 98101-1309, USA

    Allison A. Eddy, Jesús M. López-Guisa, Daryl M. Okamura & Ikuyo Yamaguchi

  2. Department of Pediatrics, University of Washington, Seattle, WA, USA

    Allison A. Eddy, Jesús M. López-Guisa, Daryl M. Okamura & Ikuyo Yamaguchi

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  1. Allison A. Eddy
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  2. Jesús M. López-Guisa
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  3. Daryl M. Okamura
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  4. Ikuyo Yamaguchi
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Correspondence to Allison A. Eddy.

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Eddy, A.A., López-Guisa, J.M., Okamura, D.M. et al. Investigating mechanisms of chronic kidney disease in mouse models. Pediatr Nephrol 27, 1233–1247 (2012). https://doi.org/10.1007/s00467-011-1938-2

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  • DOI: https://doi.org/10.1007/s00467-011-1938-2

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