Multiple variants of the peroxisome proliferator-activated receptor (PPAR)gamma are expressed in the liver of Atlantic salmon (Salmo salar)

A full-length cDNA encoding the peroxisome proliferator-activated receptor (PPAR) has for the first time been characterized from a fish species. The A tlantic salmon PPAR gamma cDNA of 2528 nucleotides (nt) was amplified from liver mRNA by reverse transcription (RT)-polymerase chain reaction (PCR). T he deduced protein of 544 amino acids (aa) shares approximately 47% overall sequence identity with mammalian PPAR gamma. The N-terminal A/B region con tains a repeated decapeptide motif and shows a low homology with other PPAR s. In contrast, the central DNA-binding domain (DBD) and the C-terminal lig and-binding domain (LBD) show a high sequence identity to mammalian and Xen opus PPAR gamma. The salmon PPAR gamma LBD contains nine additional residue s in a flexible loop that might affect ligand binding. Northern blot analys is of salmon liver RNA revealed a prominent transcript of about 1.7 kilo ba ses (kb), in addition to several mRNA species of about 2.4-2.6 kb, which is consistent with the presence of multiple putative polyadenylation sites in the 3' untranslated region (UTR) of the 2528 nt long PPAR gamma cDNA. Two additional PPAR gamma cDNAs of 1719 and 2357 nt were then isolated. The 235 7 nt long transcript encodes full-length PPAR gamma and seems to be ubiquit ously expressed in salmon, whereas the liver-specific transcript of 1719 nt encodes a truncated variant of PPAR gamma. The truncated form lacks 39 C-t erminal residues including the conserved activation function-2 (AF-2) motif , known to be associated with crucial cofactors. Three-dimensional modellin g studies indicated that the C-terminal truncation would result in importan t alterations of the ligand-binding pocket. The presence of a truncated for m with drastic changes in both ligand- and cofactor-binding sites is likely to modulate PPAR gamma activity in salmon liver. (C) 2000 Elsevier Science B.V. All rights reserved.