CHROMOSOMAL LOCALIZATION, INDUCIBILITY, TISSUE-SPECIFIC EXPRESSION AND STRAIN DIFFERENCES IN 3 MURINE PEROXISOME-PROLIFERATOR-ACTIVATED-RECEPTOR GENES

Three murine peroxisome-proliferator-activated-receptor (PPAR) genes w ere localised to chromosome 15 (PPAR alpha), chromosome 17 (PPAR beta) and chromosome 6 (PPAR gamma). The expression of the three PPAR RNAs was determined using a specific RNase protection assay. In liver RNA, PPAR alpha: was expressed at the highest level, with 20-fold lower lev els of PPAR beta, and very low levels of PPAR gamma. The three PPAR RN As showed no sex-specific differences in expression, and the levels of these transcripts were unaffected by treatment of mice with testoster one or the potent peroxisome proliferator, methylclofenapate. In agree ment with this data, the level of PPAR alpha protein in liver was unch anged after treatment of mice with methylclofenapate, Investigation of the tissue-specific distribution revealed that the PPAR alpha RNA was expressed at highest levels in liver, to moderate levels in kidney an d brown adipose tissue, and at low levels elsewhere. PPAR beta was exp ressed at moderate levels in live;, and lower levels in other tissues, including brown adipose tissue. In contrast, PPAR gamma KNA was expre ssed at low levels in liver or epididymal white adipose tissue and at very low levels elsewhere, but was expressed at high levels in brown a dipose tissue. The tissue distribution of these receptors suggests an important role in lipid metabolism and toxicity for individual members of the PPAR family. The expression of PPAR alpha and PPAR beta RNAs w as examined in 13 strains of mice, and the levels of expression varied within a fourfold range. Polymorphism in the size of PPAR alpha RNA f rom Swiss-Webster mice was detected, and shown to be due to a 2-bp mut ation in the 3' non-coding region of PPAR alpha in Swiss Webster mice.