To study the effect of DM1-associated CTG repeats on neuronal function, we developed a PC12 cell-based model that constitutively expresses the DMPK gene 3′-untranslated region with 90 CTG repeats (CTG90 cells). As CTG90 cells exhibit impaired neurite outgrowth and as microtubule-associated proteins (MAPs) are crucial for microtubule stability, we analyzed whether MAPs are a target of CTG repeats. NGF induces mRNA expression of Map2, Map1a and Map6 in control cells (PC12 cells transfected with the empty vector), but this induction is abolished for Map2 and Map1a in CTG90 cells. MAP2 and MAP6/STOP proteins decrease in NGF-treated CTG90 cells, whereas MAP1A increases. Data suggest that CTG repeats might alter somehow the expression of MAPs, which appears to be related with CTG90 cell-deficient neurite outgrowth. Decreased MAP2 levels found in the hippocampus of a DM1 mouse model indicates that targeting of MAPs expression by CTG repeats might be relevant to DM1.
Bibliographical noteFunding Information:
Acknowledgments This study was supported by the Muscular Dystrophy Association, Inc. Grant No. MDA-3693. Prisiliana Vélazquez-Bernardino PhD student was supported by CONACyT, control number: 185951. We are in debt with Dr. Christophe Bosc (INSERM, France) and Dr. Manuel Hernández (Cinvestav, México) for providing us with the anti-MAP6/STOP and anti-actin antibodies, respectively.
Copyright 2012 Elsevier B.V., All rights reserved.
All Science Journal Classification (ASJC) codes
- Molecular Biology