Peroxisome proliferator-activated receptor (PPAR) b}d is ubiquitously

expressed, but the level of expression differs markedly

between different cell types. In order to determine the molecular

mechanisms governing PPARb}d gene expression, we

have isolated and characterized the mouse gene encoding

PPARb}d. The gene spans approx. 41 kb and comprises 11 exons

of which the six exons located in the 3«-end of the gene are

included in all transcripts. Primer-extension and 5«-rapid ampli-

®cation of cDNA ends experiments revealed the presence of

multiple transcription start points and splice variants, originating

from the use of at least four different promoters. One of these

transcription start points was found to be used predominantly in

all tissues examined. Initiation from this major transcription

start point gives rise to a transcript with a 548 nt 5«-untranslated

leader containing eight upstream AUG codons. We show that

the presence of the 548 nt leader resulted in a low translational

efficiency of the corresponding PPARb}d mRNA and propose,

based on structural features of the 5«-untranslated region, that

translational initiation may be mediated via an internal ribosome

entry site-dependent mechanism.