Expanded CTG repeats inhibit neuronal differentiation of the PC12 cell line.
Myotonic dystrophy (DM) is a dominant neuromuscular disorder caused by the expansion of trinucleotide CTG repeats in the 3-untranslated region (3'-UTR) of the MtPK gene. Although DM-associated mental retardation suggests that neuronal functions are disturbed by the expansion mutation, the effect of this alteration in neuronal cells has not been approached. In this study we established stable transfectans of PC12 neuronal cell line expressing the reporter gene CAT alone (empty-vector clone) or fused to the MtPK 3'-UTR with 5, 60, or 90 CTG repeats (CTG5, CTG60, and CTG90 clones, respectively). CTG90 cells exhibited a suppression of NGF-induced neuronal differentiation while empty-vector, CTG5 and CTG60 clones differentiated normally. CTG90 cells displayed normal activation of early differentiation markers, ERK1/2, but the up-regulation of the late marker MAP2 was dramatically reduced. Our neuronal cell system provides the first information of how the mutant MtPK 3'-UTR mRNA affects neuronal functions.
Quintero-Mora
María Leonor
ML
Departamento de Genética y Biología Molecular, Centro de Investigación y Estudios Avanzados del IPN, Avenida Instituto Politécnico Nacional 2508, Apartado Postal 14-740, C.P. 07000 Mexico D.F., Mexico.
Depardon
Francisco
F
JamesWaring
Robert G Korneluk
Cisneros
Bulmaro
B
D020413:3' Untranslated Regions; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002999:Clone Cells; D009223:Myotonic Dystrophy / Q000235:genetics; D065636:Myotonin-Protein Kinase; D009474:Neurons / Q000166:cytology*; D016716:PC12 Cells; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018911:Trinucleotide Repeats
D020413:3' Untranslated Regions; D012333:RNA, Messenger; D011494:Protein Kinases; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases