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

INTRODUCTION: Spinal muscular atrophy (SMA) is a devastating genetic disease in childhood and is caused by the absence of functional SMN protein, which leads to impairments of cytoskeleton, especially in neurons. Dysregulation of actin dynamics have been linked to SMA pathomechanisms, 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.
METHODS: By focusing 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 patient and spinal cords of SMA mice. We found altered expression of microtubule-associated protein 2 (MAP2), which was validated by real time RT-PCR using SMN knock-down NSC34 cell line and severe SMA mouse model.
RESULTS: We showed that expression of MAP2 gene was significantly upregulated in both expression arrays. Upregulation was also detected in brain and spinal cord tissues of severe SMA mice at different developmental stages.
DISCUSSION AND CONCLUSION: Our findings suggest that microtubule regulatory proteins may be altered in SMN depleted cells and further research are needed to elucidate contribution of dysregulated microtubule dynamics to SMA.