ABSTRACT
Over the past decade, significant breakthroughs have been made in identifying genes critical in regulating energy balance and obesity, and most of these advances have relied upon the utilization of both forward and reverse genetics in mice. Forward genetics goes from phenotype to genotype by means of positional cloning and candidate gene analyses, and this approach has led to the cloning of leptin and leptin receptor genes. Conversely, reverse genetics goes from genotype to phenotype by means of gene targeting, transgenic manipulation of gene expression, or expression knockdown by RNA interference. Reverse genetics in rodents has revealed the critical role the central melanocortin system plays in energy homeostasis and its function in obesity development. To date, mutations in the central melanocortin pathways constitute the most prevalent forms of monogenic obesity seen in rodents and humans.
