Moxham C M, Hod Y, Malbon C C
Department of Molecular Pharmacology, State University of New York (SUNY)/Stony Brook 11794-8651.
Science. 1993 May 14;260(5110):991-5. doi: 10.1126/science.8493537.
Guanosine triphosphate-binding regulatory proteins (G proteins) are key elements in transmembrane signaling and have been implicated as regulators of more complex biological processes such as differentiation and development. The G protein G alpha i2 is capable of mediating the inhibitory control of adenylylcyclase and regulates stem cell differentiation to primitive endoderm. Here an antisense RNA to G alpha i2 was expressed in a hybrid RNA construct whose expression was both tissue-specific and induced at birth. Transgenic mice in which the antisense construct was expressed displayed a lack of normal development in targeted organs that correlated with the absence of G alpha i2. The loss of G alpha i2 expression in adipose tissue of the transgenic mice was correlated with a rise in basal levels of adenosine 3',5'-monophosphate (cAMP) and the loss of receptor-mediated inhibition of adenylylcyclase. These data expand our understanding of G protein function in vivo and demonstrate the necessity for G alpha i2 in the development of liver and fat.
鸟苷三磷酸结合调节蛋白（G蛋白）是跨膜信号传导的关键元件，并被认为是更复杂生物过程（如分化和发育）的调节因子。G蛋白Gαi2能够介导对腺苷酸环化酶的抑制性控制，并调节干细胞向原始内胚层的分化。在此，在一种杂交RNA构建体中表达了针对Gαi2的反义RNA，该构建体的表达具有组织特异性且在出生时被诱导。表达反义构建体的转基因小鼠在靶向器官中表现出正常发育缺失，这与Gαi2的缺失相关。转基因小鼠脂肪组织中Gαi2表达的缺失与3',5'-单磷酸腺苷（cAMP）基础水平的升高以及受体介导的腺苷酸环化酶抑制作用的丧失相关。这些数据扩展了我们对G蛋白在体内功能的理解，并证明了Gαi2在肝脏和脂肪发育中的必要性。
