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

To determine the physiological roles of peroxisome proliferator-activated receptor 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 persisted postnatally. Gonadal adipose stores were smaller, and constitutive mRNA 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 epidermal 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. Inflammation induced by TPA in the skin was lower in wild-type mice fed sulindac than 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.