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

Aim: Spinal muscular atrophy (SMA) is a devastating genetic disease in childhood andff is caused by the absence of functional survival motor neuron (SMN) protein, which leads to impairments of the cytoskeleton, especially in neurons. Dysregulation of actin dynamics have been linked to SMA patho mechanisms, however involvement of altered microtubule dynamics is largely unknown. In this study, we investigated differentially 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 were previously performed with induced pluripotent stem cell-derived motor neurons of SMA patients and the spinal cords of SMA mice. We found altered expressions of microtubule-associated protein 2 (MAP2), which was validated by real time reverse-transcription polymerase chain reaction 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 also detected 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 needed to elucidate the contribution of dysregulated microtubule dynamics towards SMA.