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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 831092, 7 pages
http://dx.doi.org/10.1155/2011/831092
Research Article

Muscle Atrophy and Motor Neuron Degeneration in Human NEDL1 Transgenic Mice

1Division of Biochemistry and Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-Ku, Chiba 260-8717, Japan
2Center for Functional Genomics, Hisamitsu Pharmaceutical Co., Inc., Chiba 260-8717, Japan
3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan

Received 18 June 2010; Accepted 25 August 2010

Academic Editor: Oreste Gualillo

Copyright © 2011 Lin Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease. Approximately 20% cases of familial ALS show the mutation in the superoxide dismutase-1 (SOD1) gene. We previously demonstrated that homologue to E6AP carboxyl terminus- (HECT-) type ubiquitin protein E3 ligase (NEDL1) physically bind to mutated SOD1 protein but not wild-type SOD1 and promote the degradation of mutated SOD1 protein through ubiquitin-mediated proteasome pathway. To further understand the role of NEDL1 involved in the pathogenesis of familial ALS, we generated transgenic mice with human NEDL1 cDNA. The transgenic mice with human NEDL1 expression showed motor dysfunctions in rotarod, hanging wire, and footprint pattern examination. Histological studies indicated degeneration of neurons in the lumbar spinal cord and muscle atrophy. The number of activated microglia in the spinal cord of transgenic mice was significantly higher than that of wild-type mice, suggesting that inflammation might be observed in the spinal cord of transgenic mice. In conclusion, these findings suggest that the human NEDL1 transgenic mice might develop ALS-like symptoms, showing signs of motor abnormalities, accompanied with significant reduction in muscle strength.