Structural organization of mouse peroxisome proliferator-activated receptor γ (mPPARγ) gene: Alternative promoter use and different splicing yield two mPPARγ isoforms

To gain insight into the regulation of expression of peroxisome proliferator-activated receptor (PPAR) isoforms, we have determined the structural organization of the mouse PPAR γ (mPPARγ) gene. This gene extends >105 kb and gives rise to two mRNAs (mPPARγ1 and mPPARγ2) that differ at their 5' ends. The mPPARγ2 cDNA encodes an additional 30 amino acids N-terminal to the first ATG codon of mPPARγ1 and reveals a different 5' untranslated sequence. We show that mPPARγ1 mRNA is encoded by eight exons, whereas the mPPARγ2 mRNA is encoded by seven exons. Most of the 5' untranslated sequence of mPPARγ1 mRNA is encoded by two exons, whereas the 5' untranslated sequence and the extra 30 N-terminal amino acids of mPPARγ2 are encoded by one exon, which is located between the second and third exons coding for mPPARγ1. The last six exons of mPPARγ2 gene code for identical sequences in mPPARγ1 and mPPARγ2 isoforms. The mPPARγ1 and mPPARγ2 isoforms are transcribed from different promoters. The mPPARγ gene has been mapped to chromosome 6 E3-F1 by in sire hybridization using a biotin-labeled probe. These results establish that at least one of the PPAR genes yields more than one protein product, similar to that encountered with retinoid X receptor and retinoic acid receptor genes. The existence of multiple PPAR isoforms transcribed from different promoters could increase the diversity of ligand and tissue-specific transcriptional responses.