Wang N D, Finegold M J, Bradley A, Ou C N, Abdelsayed S V, Wilde M D, Taylor L R, Wilson D R, Darlington G J
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Science. 1995 Aug 25;269(5227):1108-12. doi: 10.1126/science.7652557.
Mice homozygous for the targeted deletion of the c/ebp alpha gene, which expresses the CCAAT/enhancer-binding protein alpha (C/EBP alpha), did not store hepatic glycogen and died from hypoglycemia within 8 hours 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, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, was delayed. The hepatocytes and adipocytes of the mutant mice failed to accumulate lipid and the expression of the gene for uncoupling protein, the defining marker of brown adipose tissue, was reduced. This study demonstrates that C/EBP alpha is critical for the establishment and maintenance of energy homeostasis in neonates.
c/ebpα基因靶向缺失的纯合子小鼠，该基因表达CCAAT/增强子结合蛋白α（C/EBPα），出生后8小时内无法储存肝糖原并死于低血糖。在这些突变小鼠中，糖原合酶信使核糖核酸的量为正常量的50%至70%，两种糖异生酶（磷酸烯醇丙酮酸羧激酶和葡萄糖-6-磷酸酶）基因的转录诱导延迟。突变小鼠的肝细胞和脂肪细胞无法积累脂质，解偶联蛋白（棕色脂肪组织的标志性标志物）基因的表达降低。这项研究表明，C/EBPα对新生儿能量稳态的建立和维持至关重要。
