Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta)

To determine the physiological roles of peroxisome proliferator-activated r eceptor beta (PPAR beta), null mice were constructed by targeted disruption of the ligand binding domain of the murine PPAR beta gene. Homozygous PPAR beta-null term fetuses were smaller than controls, and this phenotype pers isted postnatally. Gonadal adipose stores were smaller, and constitutive mR NA levels of CD36 were higher, in PPAR beta-null mice than in controls. In the brain, myelination of the corpus callosum was altered in PPAR beta-null mice. PPAR beta was not required for induction of mRNAs involved in epider mal differentiation induced by O-tetradecanoylphorbol-13-acetate (TPA). The hyperplastic response observed in the epidermis after TPA application was significantly greater in the PPAR beta-null mice than in controls. Inflamma tion induced by TPA in the skin was lower in wild-type mice fed sulindac th an in similarly treated PPAR beta-null mice. These results are the first to provide in vivo evidence of significant roles for PPAR beta in development , myelination of the corpus callosum, lipid metabolism, and epidermal cell proliferation.