Chromosomal Localisation, Inducibility, Tissue‐Specific Expression and Strain Differences in Three Murine Peroxisome‐Proliferator‐Activated‐Receptor Genes

Abstract

Three murine peroxisome-proliferator-activated-receptor (PPAR) genes were localised to chromosome 15 (PPARα), chromosome 17 (PPARβ) and chromosome 6 (PPARγ). The expression of the three PPAR RNAs was determined using a specific RNase protection assay. In liver RNA, PPARα was expressed at the highest level, with 20-fold lower levels of PPARβ, and very low levels of PPARγ. The three PPAR RNAs showed no sex-specific differences in expression, and the levels of these transcripts were unaffected by treatment of mice with testosterone or the potent peroxisome proliferator, methylclofenapate. In agreement with this data, the level of PPARα protein in liver was unchanged after treatment of mice with methylclofenapate. Investigation of the tissue-specific distribution revealed that the PPARα RNA was expressed at highest levels in liver, to moderate levels in kidney and brown adipose tissue, and at low levels elsewhere. PPARβ was expressed at moderate levels in liver, and lower levels in other tissues, including brown adipose tissue. In contrast, PPARγ RNA was expressed at low levels in liver or epididymal white adipose tissue and at very low levels elsewhere, but was expressed at high levels in brown adipose 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 PPARα and PPARβ RNAs was examined in 13 strains of mice, and the levels of expression varied within a fourfold range. Polymorphism in the size of PPARα RNA from Swiss-Webster mice was detected, and shown to be due to a 2-bp mutation in the 3′ non-coding region of PPARα in Swiss Webster mice.