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Kilian Kürten, Anne-Christin Gude, Aimo Samuel Christian Epplen, Jan Philipp Stein, Carsten Theiß, Veronika Matschke

• Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis (ALS) and in animal models, suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS. Dysregulation of Kinesin-family-member 5\(\alpha\) (Kif5\(\alpha\)), a neuron-specific isoform of heavy chain kinesin family, has been described in several neurological disorders, in humans and animal models, including ALS. In this study, we determined Kif5\(\alpha\) expression by gene sequencing, quantitative reverse transcription-polymerase chain reaction, and western blot assay in the cervical spinal cord of wobbler mice and immunofluorescence staining in dissociated cultures of the ventral horn. Further, we observed the distribution of Kif5\(\alpha\) and mitochondria along motor neuronal branches by confocal imaging. Our results showed that Kif5\(\alpha\) expression was greatly dysregulated in wobbler mice, which resulted in altered distribution of Kif5\(\alpha\) along motor neuronal branches with an abnormal mitochondrial distribution. Thus, our results indicate that dysregulation of Kif5 and therefore abnormal transport in motor neuronal branches in this ALS model could be causative for several pathological findings at the cellular level, like misallocation of cytoskeletal proteins or organelles like mitochondria.