Utility of Rats as Disease Models
From a physiological perspective, the liver metabolism of rats—in terms of the number and type of liver enzymes—is more similar to humans. The rat is often favored by researchers due to its morphology, which makes it easier to surgically manipulate, dose, and collect samples from. As such, rats are preferred over mice for many ADMET studies.
Physiologists and pathologists may prefer the anatomical characteristics of rats as well. For example, the cardiovascular system of the rat is more similar to humans as compared to the mouse. This, coupled with its larger size, makes the rat a preferred cardiovascular model for many applications.
Cardiovascular research, however, is not the only therapeutic area in which rats are often considered superior models to mice. Rats have many behavioral and cognitive characteristics similar to humans as well, and hold the promise to more closely model certain psychotherapeutic and neurological disorders such as Parkinson disease, Alzheimer disease, schizophrenia, and autism.
While there have been many types of genetically engineered mice created to model these conditions, the mouse models used to date are often criticized for their lack of predictivity relative to the human disease. As such, findings often fail to result in target validation and successful translation to disease-modifying therapies in humans.
So, if rats are more like humans physiologically and anatomically, and are better models in certain therapeutic areas, why have they been in the background for so long?