Neuromuscular Junction Reinnervation after Injury... a Novel Role for Tbx21
Curtis Broberg, BS, Washington University, Saint Louis, MO, Albina Jablonka-Shariff, PhD, Plastic Surgery, Washington University in St. Louis, Saint Louis, MO and Alison K Snyder-Warwick, MD, Washington University School of Medicine, Saint Louis, MO
Introduction:
Terminal Schwann cells (tSCs) serve as critical regulators of neuromuscular junction (NMJ) function through roles in synaptogenesis, maintenance, and repair after injury. A potential marker exhibiting enhanced expression in these cells, Tbx21, is a transcription factor classically associated with T cells and with recruitment of immune elements. The purpose of this study was to characterize the effects of Tbx21 absence at the NMJ during the reinnervation process following injury.
Materials and Methods:
Wild Type (WT) and Tbx21-/- mice underwent sciatic nerve transection and repair. Morphometric analysis of NMJ reinnervation was conducted on mice at 2, 3, 4, and 6 weeks and 6 months after nerve injury and repair. Full NMJ reinnervation was defined as >75% coverage of acetylcholine receptors by axons. Functional assessments of muscle recovery were performed with muscle force testing at the same time points. A minimum of 3 mice were evaluated in each group, and over 1000 NMJs were evaluated morphologically.
Results:
Tbx21-/- mice showed significantly lower levels of fully reinnervated NMJs compared to WT mice at each time point tested. At 2 weeks post-injury and repair, 7% of NMJs in Tbx21-/- mice achieved full reinnervation compared to 33% of NMJs in WT mice (p<0.001). Full reinnervation occurred in 18% of NMJs in Tbx21-/- mice compared to 50% of NMJs in WT mice at 4 weeks (p<0.001). At 6 weeks post-injury and repair, 52% of NMJs were fully reinnervated in Tbx21-/- mice compared to 77% of NMJs in WT mice (p<0.05). Tbx21-/- mice had significantly diminished muscle force compared to WT mice at every time point beyond 3 weeks. Tbx21-/- mice generated 56.4 ± 13.8% of the muscle force generated by WT mice at 4 weeks post-injury and repair and 52.6 ± 27.7% of WT at 6 weeks. By 6 months post-injury and repair, Tbx21-/- mice generated 76.7% ±10.3% the muscle force of WT mice.
Conclusions:
These results indicate that Tbx21 plays an important role in NMJ reinnervation, both histologically and functionally.
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