The genomic structure and the expression profile of the Xenopus laevis transthyretin gene

Transthyretin (TTR) is a major thyroid hormone-binding protein in the amphibian tadpole whose plasma mRNA and protein levels are altered during metamorphosis. While the temporal and spatial expression patterns and genomic structure of the TTR gene are well studied in higher vertebrates, detailed expression pattern in the extrahepatic tissues, the transcriptional regulation, and the genomic structure have not yet been identified in amphibians. In this study, we attempted to elucidate these mechanisms. Here, we determined the genomic structure of the Xenopus laevis TTR gene including 5′-flanking regions, and examined TTR expression patterns in several tissues. The TTR gene of X. laevis is composed of 4 exons and 3 introns, and the nucleotide sequence of intron 1 is not similar to that previously reported. This suggests that the TTR gene of X. laevis was duplicated and the gene cloned in this study was the other copy of previously reported gene. We also found that TTR was primarily transcribed in the liver of both tadpoles and adults. In the adult liver, TTR transcripts were more abundant in males than females. In higher vertebrates, the expression of TTR is controlled by several transcription factors including forkhead box A2 (FoxA2). However, in the X. laevis liver, FoxA2 expression patterns were not similar to TTR. We also found that exogenous FoxA2 increased the X. laevis TTR promoter-driven luciferase activity. These results suggest that, in amphibian, the expression of TTR is regulated partially by FoxA2, and that another system may exist to control TTR expression.

► We determined amphibian transthyretin gene structure including regulatory regions. ► The expression of transthyretin showed distinct pattern in liver, kidney, and eye. ► In adult liver, sexual difference in expression of transthyretin was observed. ► Forkhead box A2 positively regulated the expression of transthyretin.