Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes

Abstract

The rat has been used for a long time as the model of choice in several biomedical disciplines. Numerous inbred strains have been isolated, displaying a wide range of phenotypes and providing many models of human traits and diseases. Rat genome mapping and genomics was considerably developed in the last decades. The availability of these resources has stimulated numerous studies aimed at discovering disease genes by positional identification. Numerous rat genes have now been identified that underlie monogenic or complex diseases and remarkably, these results have been translated to the human in a significant proportion of cases, leading to the identification of novel human disease susceptibility genes, helping in studying the mechanisms underlying the pathological abnormalities and also suggesting new therapeutic approaches. In addition, reverse genetic tools have been developed. Several genome-editing methods were introduced to generate targeted mutations in genes the function of which could be clarified in this manner [generally these are knockout (KO) mutations]. Furthermore, even when the human gene causing a disease is identified, mutated rat strains (in particular KO strains) were created to analyze the gene function and the disease pathogenesis. Today, about 300 rat genes have been identified as underlying diseases or playing a key role in critical biological processes that are altered in diseases. This article provides the reader with an inventory of these genes.