Induction of G alpha i2-specific antisense RNA in vivo inhibits neonatal growth.
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.
Moxham
C M
CM
Department of Molecular Pharmacology, State University of New York (SUNY)/Stony Brook 11794-8651.
Hod
Y
Y
Malbon
C C
CC
D000273:Adipose Tissue / Q000254:growth & development* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001483:Base Sequence; D001835:Body Weight; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006128:Growth / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000254:growth & development / Q000378:metabolism; D008099:Liver / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics*; D014162:Transfection
D016372:RNA, Antisense; D019204:GTP-Binding Proteins; D010729:Phosphoenolpyruvate Carboxykinase (GTP)