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The laboratory rat (Rattus norvegicus) is a key tool for the study of medicine and pharmacology for human health. A large database of phenotypes for integrated fields such as cardiovascular, neuroscience, and exercise physiology exists in the literature. However, the molecular characterization of the genetic loci that give rise to variation in these traits has proven to be difficult. Here we show how one obstacle to progress, the fine-mapping of quantitative trait loci (QTL), can be overcome by using an outbred population of rats. By use of a genetically heterogeneous stock of rats, we map a locus contributing to variation in a fear-related measure (two-way active avoidance in the shuttle box) to a region on chromosome 5 containing nine genes. By establishing a protocol measuring multiple phenotypes including immunology, neuroinflammation, and hematology, as well as cardiovascular, metabolic, and behavioral traits, we establish the rat HS as a new resource for the fine-mapping of QTLs contributing to variation in complex traits of biomedical relevance.The rat has for long been a favored organism for physiological and behavioral analyses and is increasingly attracting the attention of geneticists (Jacob and Kwitek 2002). Over the last century, a wealth of disease models have been developed, which compared with the mouse have proved easier to analyze at an organ and cellular level because of the rat's larger size. Rat models of cardiovascular disease, inflammatory diseases, and susceptibility to cancer and toxic substances have been crucial in understanding the biology of common human disorders. The rat has also been a focus of classical neuroanatomical studies and electrophysiological slice studies; rat experiments have been critical for understanding many neurobiological processes, including learning and memory, and for providing models for the neuropsychology of human behavioral disorders (Weiss and Feldon 2001).

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