Abstract
The laboratory 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 causal 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 mutations]. Furthermore, even when the human gene causing a disease had been identified without resorting to a rat model, mutated rat strains (in particular KO strains) were created to analyze the gene function and the disease pathogenesis. Today, over 350 rat genes have been identified as underlying diseases or playing a key role in critical biological processes that are altered in diseases, thereby providing a rich resource of disease models. This article is an update of the progress made in this research and provides the reader with an inventory of these disease genes, a significant number of which have similar effects in rat and humans.
Highlights
Why map and identify genes for rat disease phenotypes or related traits? As already pointed out, the laboratory rat (Rattus norvegicus) is more than a big mouse
The core of this article is a list of the diseases and related traits or phenotypes the causal gene of which was identified in the rat (Table 1)
Listed are the phenotypes uncovered by reverse genetics methods, either by ENU-mutagenesis followed by selection of the desired mutated gene, or by targeted gene editing
Summary
Why map and identify genes for rat disease phenotypes or related traits? As already pointed out, the laboratory rat (Rattus norvegicus) is more than a big mouse. Rat models of monogenic traits and diseases have been isolated but the rat has essentially been a key model for studies of complex traits in fields such as physiology, cardiovascular and diabetes. There is extensive overlap between human breast and rat mammary cancer susceptibility genomic regions and “the laboratory rat will continue to be an important model organism for researching genetically determined mechanisms of mammary cancer susceptibility that may translate directly to human susceptibility” [13]. Rats have significant anatomical and behavioral advantages over mice, because they are more sociable and skilled and have complex cognitive abilities; this wider range of social behaviors and a richer acoustic communication system confer the rat advantages in comparison to mouse models to study neuro-developmental disorders and in particular autism [14, 15]. The rat provides one with reliable models of human traits or diseases [3, 8, 11–17] (multiple details emphasizing the value of rat models can be found in these articles)
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