Positional cloning of rat mutant genes reveals new functions of these genes

Abstract

The laboratory rat (Rattus norvegicus) is a key model organism for biomedical research. Rats can be subjected to strict genetic and environmental controls. The rat's large body size is suitable for both surgical operations and repeated measurements of physiological parameters. These advantages have led to the development of numerous rat models for genetic diseases. Forward genetics is a proven approach for identifying the causative genes of these disease models but requires genome resources including genetic markers and genome sequences. Over the last few decades, rat genome resources have been developed and deposited in bioresource centers, which have enabled us to perform positional cloning in rats. To date, more than 100 disease-related genes have been identified by positional cloning. Since some disease models are more accessible in rats than mice, the identification of causative genes in these models has sometimes led to the discovery of novel functions of genes. As before, various mutant rats are also expected to be discovered and developed as disease models in the future. Thus, the forward genetics continues to be an important approach to find genes involved in disease phenotypes in rats. In this review, I provide an overview the development of rat genome resources and describe examples of positional cloning in rats in which novel gene functions have been identified. Rat Resource and Research Center (RRRC)The Rat Resource and Research Center (RRRC, http://www.rrrc.us/) is managed by the University of Missouri. The RRRC's major services are to curate valuable rat lines for cryopreservation and rederivation, as well as to distribute rat strains. The Center's research is focused on improving cryopreservation and in vitro fertilization, generating new rat models, and characterizing the gut microbiota of rat models. The RRRC also provides colony management and breeding services, genetic testing, and microinjection services. Recently, a total of ten Cre rat lines were generated, including eight for neural-specific and two for cardiovascular-specific Cre expression [10].