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Science 14 May 1993:
Vol. 260. no. 5110, pp. 991 - 995
DOI: 10.1126/science.8493537
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Articles

Science, Vol 260, Issue 5110, 991-995
Copyright © 1993 by American Association for the Advancement of Science

articles

Induction of G alpha i2-specific antisense RNA in vivo inhibits neonatal growth

CM Moxham, Y Hod, and CC Malbon

Department of Molecular Pharmacology, State University of New York (SUNY)/Stony Brook 11794-8651.

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.


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