Physiological function of the orphans GCNF and COUP-TF

Orphan nuclear receptors are members of the nuclear receptor superfamily of ligand-activated transcription factors for which ligands and functions hav e not been identified. Since the cloning of the original orphans, ligands h ave been identified for several orphan receptors that heterodimerize with t he retinoid X receptor and are no longer classified as orphan receptors. Co nsidering the central role that nuclear receptors play in differentiation, development, metabolic regulation, homeostasis and disease, it is crucial t hat we understand the roles of the remaining orphans. However, the identifi cation of ligands for those orphans that form homodimers has proven more di fficult. Thus, to gain greater insight into the functions of orphan recepto rs, gene targeting has been used to knock out these factors and study mouse development in their absence. Here we will review the progress made in und erstanding the roles of the orphans GCNF and the COUP-TFs with the use of g ene knockouts.