Absence of alsin function leads to corticospinal motor neuron vulnerability via novel disease mechanisms

• DOI: 10.1093/hmg/ddv631
• Publication Date: 2016-02-15T01:08:50Z
• Authors: Mukesh Gautam; Javier H. Jara; Gabriella Sekerkova; Marina V. Yasvoina; Marco Martina; P. Hande Özdinler
• Keywords: Hereditary Spastic Paraplegia

Mutations in the ALS2 gene result early-onset amyotrophic lateral sclerosis, infantile-onset ascending hereditary spastic paraplegia and juvenile primary suggesting prominent upper motor neuron involvement. However, importance of alsin function for corticospinal (CSMN) health stability remains unknown. To date, four separate knockout (AlsinKO) mouse models have been generated, despite hopes mimicking human pathology, none displayed profound defects. This, however, does not rule out possibility neuronal defects within CSMN, which is easy to detect these mice. Detailed cellular analysis CSMN has hampered due their limited numbers complex heterogeneous structure cerebral cortex. In an effort visualize vivo investigate precise aspects abnormalities absence function, we generated AlsinKO-UeGFP mice, by crossing AlsinKO UCHL1-eGFP a reporter line. We find that display vacuolated apical dendrites with increased autophagy, shrinkage soma size axonal pathology even pons region. Immunocytochemistry coupled electron microscopy reveal important maintaining cytoarchitecture integrity organelles. its absence, displays selective both mitochondria Golgi apparatus. mice help understand underlying factors lead vulnerability diseases, our findings unique stability.