Investigations of Microtubule-associated Protein 2 Gene Expression in Spinal Muscular Atrophy

Özet

Aim: Spinal muscular atrophy (SMA) is a devastating genetic disease in childhood andff is caused by the absence of functional survival motorneuron (SMN) protein, which leads to impairments of the cytoskeleton, especially in neurons. Dysregulation of actin dynamics have beenlinked to SMA patho mechanisms, however involvement of altered microtubule dynamics is largely unknown. In this study, we investigateddifferentially expressed microtubule-related genes using in vitro and in vivo SMA model systems.Materials and Methods: By focusing on microtubule-related genes, we re-analyzed publically available gene expression arrays, which werepreviously performed with induced pluripotent stem cell-derived motor neurons of SMA patients and the spinal cords of SMA mice. We foundaltered expressions of microtubule-associated protein 2 (MAP2), which was validated by real time reverse-transcription polymerase chainreaction using the SMN knock-down NSC34 cell line and the severe SMA mouse model.Results: We showed that the expression of MAP2 gene was significantly upregulated in both expression arrays. Upregulation was alsodetected in the brain and spinal cord tissues of severe SMA mice at different developmental stages.Conclusion: Our findings suggest that microtubule regulatory proteins may be altered in SMN depleted cells and further research is neededto elucidate the contribution of dysregulated microtubule dynamics towards SMA.