CLONING OF A NEW MEMBER OF THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GENE FAMILY FROM MOUSE-LIVER

Peroxisome proliferators are postulated to elicit predictable pleiotro pic responses in the liver by activating a peroxisome proliferator-act ivated receptor (PPAR). PPARs from mouse liver (mPPAR), rat liver (rPP AR), and Xenopus liver (xPPARgamma) have been cloned recently. We now report the cloning of a new member from mouse liver which we designate mPPARgamma. mPPARgamma cDNA contained an open reading frame encoding a 475-amino acid protein exhibiting 75% amino acid similarity to xPPAR gamma, while it showed only 55% identity with mPPAR. The ligand-bindin g and DNA-binding domains are best conserved between mPPARgamma, mPPAR , and xPPARgamma. Like rPPAR, mPPARgamma is able to impart peroxisome proliferator responsiveness to the promoter of peroxisomal bifunctiona l gene, which encodes the second enzyme of the peroxisomal fatty acid beta-oxidation system. Northern blot analysis revealed high expression of mPPARgamma gene in mouse liver, kidney, and heart and low expressi on in the lung, testis, brain, skeletal muscle, and spleen. In mice tr eated with ciprofibrate, a peroxisome proliferator, a 2-fold increase in mPPARgamma mRNA was observed in the liver and kidney. The presence of two PPARs in the mouse liver suggests the possibility of multiple s ignaling pathways for the peroxisome proliferator-induced pleiotropic responses.