Figure 1

THRB gene structure, location and transcriptional activity of ICR SNPs. A. Diagram of the THRB gene showing the origins of the TR β1- and TR β2-specific transcripts. The gray square represents the conserved 600 bp TR β2-specific intron control region (ICR), homologous to the mouse sequence. The location of the exonic R338W mutation in the index case of PRTH is marked by a vertical line. Major TR β1-specific 5' exons are shown, but not all variable untranslated sequences of TR β1 transcripts are included [24]. B, Luciferase reporter gene constructs, showing in the lower half of the panel the location of SNPs found in the ICR (rs6798561 α, rs17194828 β, rs2596623 γ, rs2596622 δ, rs77624520 ε). C, Transcriptional activity of the reporter constructs; genomic sequence origin, human (Hs, Homo sapiens), mouse (Mm, Mus musculus). Compared to the human promoter alone, the human promoter plus ICR gave a 10-fold increase in pituitary cell-specific luciferase expression. Constructs containing the murine promoter and ICR are included as positive controls for ICR activity. Analysis of the chimeric reporter (human promoter + mouse ICR) indicated that the ICR activity is conserved. No activity of the ICR was observed in kidney-derived HEK-293T cells (see text for details). * = significant on Tukey's post-hoc analysis.