MANZON, L.A.*; LAUDET, V.; YOUSON, J.H.: Cloning and Expression of Sea Lamprey (Petromyzon marinus) Thyroid Hormone and Retinoid X Receptors.

Sea lampreys (Petromyzon marinus) are extant representatives of an ancient group of vertebrates with a history that can be traced over 500 million years. A dramatic decline in serum thyroid hormones (TH) occurs at the onset of lamprey metamorphosis, but the significance of this decline to the initiation and progression of metamorphosis remains to be elucidated. Since, in most other vertebrates, the effects of TH are generally mediated by interactions with a thyroid hormone receptor (TR) – retinoid X receptor (RXR) heterodimer, we cloned the cDNAs for these receptors and examined their expression over the lamprey life cycle. RT-PCR and 5′ and 3′ RACE yielded full-length cDNAs for two thyroid hormone receptors (TR1 and TR2) and one retinoid X receptor (RXR). The deduced amino acid sequences of these lamprey receptors were approximately 85-88% similar to those of other vertebrates. Northern blotting using RNA from several larval and adult tissues indicated that the expression of TR1, but not TR2, is tissue- and stage-specific. Similar TR expression patterns are also observed in other metamorphosing vertebrates. Our lamprey RXR contains a deletion in the hinge and ligand-binding domains of the receptor, but its expression patterns have not yet been determined. The results of these cloning and expression studies indicate that the sequence, and perhaps the function, of these receptors has been conserved during vertebrate evolution. Furthermore, knowledge of the expression of these receptors aids our understanding of the role of TH in lamprey metamorphosis and provides insights into the molecular mechanisms involved in this developmental event. Funded by NSERC.