Using Genetic and Species Diversity to Tackle Kidney Disease

Abstract

Progress in the identification of causal genes and understanding of the mechanism underlying kidney disease is hindered by the almost exclusive use of a few animal models with restrictive monogenic backgrounds that may be more resistant to kidney disease compared with humans and, therefore, poor models. Exploring the large genetic diversity in classical animal models, such as mice and rats, and leveraging species diversity will allow us to use the genetic advantages of zebrafish, Drosophila, and other species, to develop both new animal models that are more relevant to the study of human kidney disease and potential therapies.

Keywords: animal model; genetic diversity; kidney.

Figure 1.

Genetic and Species Diversity to Study Human Kidney Disease. Animal models provide a rich source of both genetic and phenotypic variability, similar to the human population. (A) By taking advantage of the unique qualities of each animal model and genetic diversity within those models, advances in understanding physiology, mechanisms, and genes underlying kidney disease can lead to new therapeutics. (B) The integration of physiological and genetic information across all species will provide a more complete picture of kidney structure and function than the study of any one model, even humans.

Figure 1.

Genetic and Species Diversity to Study Human Kidney Disease. Animal models provide a rich source of both genetic and phenotypic variability, similar to the human population. (A) By taking advantage of the unique qualities of each animal model and genetic diversity within those models, advances in understanding physiology, mechanisms, and genes underlying kidney disease can lead to new therapeutics. (B) The integration of physiological and genetic information across all species will provide a more complete picture of kidney structure and function than the study of any one model, even humans.

Figure 2.

The Power of Genetic Mapping using Diversity Outbred (DO) Mice and Heterogeneous Stock (HS) Rats. Both DO and HS models offer unique resources to map traits involved in complex disease, including kidney disease. Each population was derived by selecting eight genetically diverse inbred strains and subsequent outbreeding for many generations. Each animal from this unique resource has a unique combination of the eight founder genome and both populations show a much greater phenotypic diversity than what we observe in the founder strains. As such, these outbred rodent populations can be viewed as similar to human populations as they exhibit diverse phenotypes, including susceptibility or resistance to kidney disease, with ability to define their underlying genetic basis with high resolution using GWAS techniques.