SOD1 mouse reveals microRNA role in repairing nerve injury

A research team from the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, reported that a micro RNA (miR), specifically, miR-206, plays an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS) (Williams et al. 2010). The discovery significantly improved our understanding of ALS and how motor neurons and skeletal muscle fibers communicate at neuromuscular junctions (NMJs), and may help find new therapies for ALS and other neurological diseases.

The research team suspected that miRs play an important role in ALS because evidence indicated that they mediate muscle stress responses. So, the team compared the expression of 320 miRs between normal mice and the widely used ALS "SOD1" mouse model, JAX® Mice strain B6SJL-Tg(SOD1*G93A)dl1Gur/J (002300). They found that miR-206, a skeletal muscle-specific miR, is dramatically up-regulated in this SOD1 model, that the up-regulation coincides with the onset of ALS neurological symptoms, and that it is a consequence of muscle denervation.

Their study also revealed that whereas miR-206 is not needed to form or help mature NMJs, it is needed to form new ones after denervating injury. Mice deficient in miR-206, but otherwise normal, develop normally for at least 300 days. Although SOD1 mice that are also miR-206-deficient develop ALS at the same time as regular SOD1 mice, their disease progresses faster (after onset), and they die sooner. These findings indicated that miR-206 is beneficial during the early stages of ALS. The team also found that miR-206 mediates reinnervation of NMJs, at least partly, through the histone deacetylase 4 (HDAC4) and FGF binding protein 1 (FGFBP1) signaling pathways.

The findings by the Southwestern Medical Center researchers revealed the importance of the miR-206-HDAC4-FGFBP1 signaling pathway in maintaining NMJs and may provide opportunities for developing ALS therapies. They will also spur further studies on the functions of miRs in the development and maintenance of the nervous system and of their potential role in developing new therapies for other neurological diseases.

The Jackson Laboratory has many resources to facilitate ALS research. Visit the JAX ALS website to print a list of JAX® Mice suitable for ALS research or to download a manual on maintaining and caring for ALS mouse models.


Williams AH, Valdez G, Moresi V, Qi X, McAnally J, Elliott JL, Bassel-Duby R, Sanes JR, Olson EN. 2010. MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science 326:1549-54.