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 receptor beta (PPARbeta), null mice were constructed by targeted disruption of the ligand binding domain of the murine PPARbeta gene. Homozygous PPARbeta-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 PPARbeta-null mice than in controls. In the brain, myelination of the corpus callosum was altered in PPARbeta-null mice. PPARbeta 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 PPARbeta-null mice than in controls. Inflammation induced by TPA in the skin was lower in wild-type mice fed sulindac than in similarly treated PPARbeta-null mice. These results are the first to provide in vivo evidence of significant roles for PPARbeta in development, myelination of the corpus callosum, lipid metabolism, and epidermal cell proliferation.
Peters
J M
JM
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. jmp21@psu.edu
Lee
S S
SS
Li
W
W
Ward
J M
JM
Gavrilova
O
O
Everett
C
C
Reitman
M L
ML
Hudson
L D
LD
Gonzalez
F J
FJ
D000273:Adipose Tissue / Q000002:abnormalities*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001824:Body Constitution / Q000235:genetics*; D001831:Body Temperature / Q000235:genetics; D001921:Brain / Q000002:abnormalities / Q000473:pathology* / Q000502:physiology; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics; D005215:Fasting; D005260:Female; D006965:Hyperplasia; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009186:Myelin Sheath / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000473:pathology*; D013467:Sulindac / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018955:CD36 Antigens; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D013467:Sulindac; D013755:Tetradecanoylphorbol Acetate