[Structure of the retinoic acid receptor and its functional analysis using a mutated receptor]

RA shows a variety of actions including the teratogenicity at pharmacological doses, but its physiological roles remain unclear. Recently, receptors for RA, RARs, have been identified and shown to belong to the nuclear receptor superfamily. We introduced a mutation, which was originally identified in the thyroid hormone receptor gene, causing dominantly inherited thyroid hormone resistance, to the equivalent position in RAR, and showed that the mutated RAR demonstrated a dominant-negative phenotypes. We next expressed the mutated RAR specifically in chondrogenic cells in mice. From the analysis of mice phenotypes, we unveiled the chondrogenic cells as a novel vital RA target in skeletal development. The results simultaneously indicated that RA specifies cervical identities through the regulation of homeobox genes.