INDUCTION OF G-ALPHA(I2)-SPECIFIC ANTISENSE RNA INVIVO INHIBITS NEONATAL GROWTH

Guanosine triphosphate-binding regulatory proteins (G proteins) are ke y elements in transmembrane signaling and have been implicated as regu lators of more complex biological processes such as differentiation an d development. The G protein Galpha(i2) is capable of mediating the in hibitory control of adenylylcyclase and regulates stem cell differenti ation to primitive endoderm. Here an antisense RNA to Galpha(i2) was e xpressed in a hybrid RNA construct whose expression was both tissue-sp ecific and induced at birth. Transgenic mice in which the antisense co nstruct was expressed displayed a lack of normal development in target ed organs that correlated with the absence of Galpha(i2). The loss of Galpha(i2) expression in adipose tissue of the transgenic mice was cor related 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 Galpha(i2) in the development of liver and fat.