A RATional choice for translational research?

Abstract

Future prospects continue to be strong for research using the rat as a model organism. New technology has enabled the proliferation of many new transgenic and knockout rat strains, the genomes of more than 40 rat strains have been sequenced, publications using the rat as a model continue to be produced at a steady rate, and discoveries of disease-associated genes and mechanisms from rat experiments abound, frequently with conservation of function between rats and humans. However, advances in genome technology have led to increasing insights into human disease directly from human genetic studies, pulling more and more researchers into the human genetics arena and placing funding for model organisms and their databases under threat. This, therefore, is a pivotal time for rat-based biomedical research – a timely moment to review progress and prospects – providing the inspiration for a new Special Collection focused on the impact of the model on translational science, launched in this issue of Disease Models & Mechanisms. What disease areas are most appropriate for research using rats? Why should the rat be favoured over other model organisms, and should the present levels of funding be continued? Which approaches should we expect to yield biologically and medically useful insights in the coming years? These are key issues that are addressed in the original Research Articles and reviews published in this Special Collection, and in this introductory Editorial. These exemplar articles serve as a landmark for the present status quo after a decade of major advances using the rat model and could help to guide the direction of rat research in the coming decade.

Renal disease pathophysiology and treatment: contributions from the rat

“…We consider aspects of hypertensive renal damage, diabetic nephritis, AKI and CKD. We emphasize the utility and limitations of the rat in recapitulating features of human renal pathologies in vivo and how this model organism has shed light on complex underlying mechanisms of disease progression of therapeutic relevance – information that might ultimately lead to the development of new drug treatments and targets (Aitman et al, 2016, 2008). …”

From integrative genomics to systems genetics in the rat to link genotypes to phenotypes

“…The rat is a mammalian species with a long-established history in biomedical research, leading to its detailed phenotypic characterization. Although the mouse has been the primary model of choice for immunological phenotyping and gene-targeting studies (Jacob and Kwitek, 2002), the rat is arguably the best model for the study of cardiovascular and metabolic diseases (among other diseases; see Aitman et al, 2016) because it facilitates a more accurate analysis of clinical and cellular phenotypes in the cardiovascular system (Gauguier, 2016). For instance, traditional QTL mapping has been extremely successful in the rat: 109 QTLs have been mapped in the rat for ‘heart’ traits (compared to 29 in mouse and 14 in human) and 453 QTLs have been mapped in the rat for ‘blood pressure’ traits (compared to 40 in mouse and 77 in human) [source: Rat Genome Database (RGD), , accessed on 02/07/16].…”

NF1deficiency correlates with estrogen receptor signaling and diminished survival in breast cancer

“…The rat offers significant advantages over the mouse because of its larger size, more representative physiology to human disease, higher degree of cognition and memory, and ease of use in pharmaceutical studies. 31,32 In our study we utilized CRISPR-Cas9 gene editing capabilities to create several rat models of Nf1 deletions in order to evaluate the effect of Nf1 deficiency on tumorigenesis. The resulting Nf1 indels induced highly penetrant, aggressive mammary adenocarcinomas in multiple rat founder lines.…”