IMPAIRED ENERGY HOMEOSTASIS IN C EBP-ALPHA KNOCKOUT MICE/

Mice homozygous for the targeted deletion of the c/ebp alpha gene, whi ch expresses the CCAAT/enhancer-binding protein alpha (C/EBP alpha), d id not store hepatic glycogen and died from hypoglycemia within 8 hour s after birth. In these mutant mice, the amounts of glycogen synthase messenger RNA were 50 to 70 percent of normal and the transcriptional induction of the genes for two gluconeogenic enzymes, phosphoenolpyruv ate carboxykinase and glucose-6-phosphatase, was delayed. The hepatocy tes and adipocytes of the mutant mice failed to accumulate lipid and t he expression of the gene for uncoupling protein, the defining marker of brown adipose tissue, was reduced. This study demonstrates that C/E BP alpha is critical for the establishment and maintenance of energy h omeostasis in neonates.