Genetic Ablation of cIAP2 Results in a Protection Against Denervation-Induced Skeletal Muscle Atrophy

• Main Author: Timusk, Kristen S.
• Other Authors: Korneluk, Robert G.
• Language: en
• Published: Université d'Ottawa / University of Ottawa 2011
• Online Access: http://hdl.handle.net/10393/20160; http://dx.doi.org/10.20381/ruor-4726

Skeletal muscle atrophy occurs as a secondary result from a number of conditions such as cancer cachexia, prolonged bed rest, and AIDS. Unfortunately, the cellular and molecular mechanisms behind atrophy are still poorly understood. It was recently found that the cellular inhibitors of apoptosis (cIAP1 and cIAP2) proteins play vital, yet redundant roles in the regulation of the NF-κB pathway, which is one of the most significant signalling pathways correlated with the loss of skeletal muscle mass in a number of conditions. I asked whether cIAP2 plays a role in skeletal muscle atrophy, using a denervation model which results in a consistent and rapid loss of muscle mass over a matter of days. cIAP2-/- and wild-type mice were denervated by removing a small portion of the sciatic nerve in the mid-thigh region of one limb, while the opposite limb was used as control. Fourteen days following sciatic nerve denervation, muscle tissue was harvested and the fibre cross-sectional area measured. I demonstrate that in the cIAP2-/- mice, muscle fibre size was spared when compared with their wild-type counterparts. To further support this phenotype, western blot analyses were performed with the muscles collected, which indicated a reduction in various muscle atrophy markers in the cIAP2-/- mice compared to wild-type, further supporting the observed protective phenotype. These data suggest that cIAP2 is a key regulator of skeletal muscle atrophy.