Thyroid Hormone Receptor alpha- and beta-Knockout Xenopus tropicalis Tadpoles Reveal Subtype-Specific Roles During Development

Thyroid hormone (TH) binds TH receptor alpha (TR alpha) and beta (TR beta) to induce amphibian metamorphosis. Whereas TH signaling has beenwell studied, functional differences between TR alpha and TR beta during this process have not been characterized. To understand how each TR contributes to metamorphosis, we generated TR alpha- and TR beta-knockout tadpoles of Xenopus tropicalis and examined developmental abnormalities, histology of the tail and intestine, and messenger RNA expression of genes encoding extracellular matrix-degrading enzymes. In TR beta-knockout tadpoles, tail regression was delayed significantly and a healthy notochord was observed even 5 days after the initiation of tail shortening (stage 62), whereas in the tails of wild-type and TR beta-knockout tadpoles, the notochord disappeared after; similar to 1 day. The messenger RNA expression levels of genes encoding extracellular matrix-degrading enzymes (MMP2, MMP9TH, MMP13, MMP14, and FAP alpha) were obviously reduced in the tail tip of TR beta-knockout tadpoles, with the shortening tail. The reduction in olfactory nerve length and head narrowing by gill absorptionwere also affected. Hind limb growth and intestinal shortening were not compromised in TR beta-knockout tadpoles, whereas tail regression and olfactory nerve shortening appeared to proceed normally in TR alpha-knockout tadpoles, except for the precocious development of hind limbs. Our results demonstrated the distinct roles of TR alpha and TR beta in hind limb growth and tail regression, respectively.