Rats!

Abstract

As a model of human disease, the rat offers many advantages over the mouse and other organisms. In fact, rats were once the most widely used organism in medical research, and the successful isolation of rat ES cells will quickly expand their utilityThe Chinese calendar year of the rat lived up to its name. By the end of the year, five papers describing methods to produce pluripotent stem cells from rats had been published. Some methods are capable of providing access to the germline of the rat, which should lead to valuable models of human disease (Buehr et al., 2008;Li et al., 2008;Liao et al., 2009;Ueda et al., 2008). This marks the successful conclusion of efforts that span more than 15 years and lags almost 30 years behind the same achievement in the mouse. It is not an end but a beginning. The work now must establish the same robust targeting methodologies in the rat that are available for the mouse. The promise of induced pluripotent stem cell (iPS) technology for the rat needs to be more widely embraced. The methodology needs to be integrated into the large and expanded genomic toolbox for the rat. We think it is useful to consider the reasons that this advance may be important beyond the symbolism of prosperity that the rat embodies in the Chinese calendar. Why the rat?Given that a great deal of technology for functional genomics is available in the mouse, how important is the rat as a model organism? For the last 30 years, investigators have chosen to use mouse models because of the technologies that are available. Now that the same technologies are at hand with the rat, scientists will be able to choose the most appropriate model based on the biology, whether it is rat, mouse or both. Even though these species look similar, there are millions of years of evolution separating the rat and mouse, and there are significant differences between them.As a model of human disease, the rat offers many advantages over the mouse and other organisms. In fact, rats were once the most widely used organism in medical research, and the successful isolation of rat ES (embryo-derived stem) cells will quickly expand their utility. The rat is an excellent model for cardiovascular disease, particularly for stroke and hypertension, and there are a variety of genetic stocks that are ideal for these studies. The physiology is easier to monitor in the rat and, over time, a volume of data has developed that will take years to be replicated in the mouse. Moreover, in many cases, the physiology is more like the corresponding human condition. In studies of cognition and memory, the rat is superior to other models because the physiological systems involved in learning and memory have been so extensively studied in this animal. The rat is more intelligent than the mouse and is capable of learning a wider variety of tasks that are important to cognitive research. The size of the animal enhances its use as a disease model, not just because of the ability to perform surgical procedures, but also because of the proportional size of impor...

Generation of genetically modified rats from embryonic stem cells

“…Despite this history, rats lag far behind mice in functional genetic studies and the generation of knockout animal models reflecting human diseases because of the absence of germline-competent rat ES cells, which are vital in a reverse genetics approach (2,3). Recently, gene-targeting rats were created by the zinc finger nuclease strategy (4).…”

Integrated Transcriptomic-Proteomic Analysis Using a Proteogenomic Workflow Refines Rat Genome Annotation

“…Novel protein forms could add value in understanding such complex neurological diseases. Interestingly, genome annotations could also be refined for genes implicated in diseases affecting tissues other than the brain such as cardiovascular disease and breast cancer, for both of which rats are considered to be an excellent model system (39). Novel proteoforms for such genes could add microglia-specific functional roles to these genes.…”

The Comparison of Rat and Human Intestinal and Hepatic Glucuronidation of Enterolactone Derived from Flaxseed Lignans

“…In comparison with other animal models, rat offers many advantages and is an excellent model for human diseases because of the well-characterized physiology that is more like the corresponding human conditions 150 . A volume of data has developed and numerous experimental protocols are well established, which enables an easier way to obtain information to design experiments, make comparisons between studies, and to extrapolate from in vitro to in vivo and from animals to humans.…”