Highly specific inhibition of IGF-I-stimulated differentiation by an antisense oligodeoxyribonucleotide to myogenin mRNA. No effects on other actions of IGF-T.
Myogenin is a member of the recently discovered family of muscle determination genes that have been shown to induce myogenic differentiation in nonmuscle cells and to be closely correlated with terminal differentiation in myoblasts. An antisense oligodeoxyribonucleotide complementary to the first five codons of myogenin blocks the stimulation of terminal myogenic differentiation by insulin-like growth factor I (IGF-I). This effect exhibits a high degree of specificity on two levels; exchanging the positions as few as 2 of the 15 bases in the oligomer abolishes its activity, and none of the other processes stimulated by IGF-I in L6A1 myoblasts are affected by the presence of the oligomer. These processes include cell proliferation as well as incorporation of leucine, uridine, and thymidine into macromolecules. The specificity, ease, and convenience of this approach indicates its potential applicability to studies on actions of other putative controlling genes in other systems.
Biology Department, Syracuse University, New York 13244.
J R
JR
Florini
D Z
DZ
Ewton
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003402:Creatine Kinase / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D018008:Myogenin; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D015345:Oligonucleotide Probes; D012313:RNA / Q000235:genetics; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics*; D051381:Rats; D013002:Somatomedins / Q000494:pharmacology*
D009124:Muscle Proteins; C503803:Myog protein, rat; D018008:Myogenin; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D016372:RNA, Antisense; D012333:RNA, Messenger; D013002:Somatomedins; D012313:RNA; D007334:Insulin-Like Growth Factor I; D003402:Creatine Kinase