TR4 is a new member of the nuclear hormone receptor family. This receptor is highly conserved in rat and human, but an in-frame insertion of 19 amino acid residues in the amino-terminal (A/B) region was found in the human homolog, which we refer to as hTR4α1. By reverse transcription-PCR (RT-PCR) we have identified a human TR4 mRNA (hTR4α2) that is analogous in size and sequence to the reported rat TR4. RT-PCR analysis using total RNA derived from various rat tissues revealed a new rat TR4 transcript, referred to as rTR4α1, which is homologous to hTR4α1 since it contains the extra 19 amino acids in the A/B region. The two rat transcripts showed a differential tissue distribution. Analysis of the exon-intron organization of the hTR4 A/B region showed that the 19-amino-acid peptide insert in hTR4α1 was encoded by a separate exon, indicating that hTR4α1 and hTR4α2 transcripts were produced by the differential usage of the exon. RT-PCR analysis revealed that both hTR4α1 and hTR4α2 were detectable in brain, placenta, and ovary. In contrast, the human ovarian cancer cell line, PA1, failed to express hTR4α1. By fluorescence in situ hybridization, we have mapped the hTR4 gene to 3p25, a region deleted in some forms of cancer.
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