Runx1 Limits Atrophy

See allHide authors and affiliations

Science's STKE  26 Jul 2005:
Vol. 2005, Issue 294, pp. tw272
DOI: 10.1126/stke.2942005tw272

Although muscle disuse causes decreases in myofiber size and function, or atrophy, the cells rarely degenerate or undergo apoptosis. Wang et al. report that the transcriptional regulator Runx1 (also known as AML1), which is abundant in developing and degenerated muscle but absent from mature, innervated muscle, regulates a set of genes that counter myofibrillar disorganization and autophagy. Mice in which runx1 was selectively inactivated in skeletal muscle after birth exhibited more extreme atrophy following muscle denervation than did control mice. In addition, loss of Runx1 resulted in structural abnormalities and the accumulation of autophagic vacuoles in the denervated muscle, which were not observed in denervated muscle from wild-type mice. Microarray analysis indicated that 29 genes were controlled by Runx1 and that Runx1 was not simply activating the same genes that respond to innervation. The analysis of these genes may provide insight valuable for understanding muscle-wasting disease. Furthermore, Runx1 appears to activate a pathway that actively opposes atrophy, thereby preventing irreversible muscle damage following periods of disuse.

X. Wang, C. Blagden, J. Fan, S. J. Nowak, I. Taniuchi, D. R. Littman, S. J. Burden, Runx1 prevents wasting, myofibrillar disorganization, and autophagy of skeletal muscle. Genes Dev. 19, 1715-1722 (2005). [Abstract] [Full Text]

Stay Connected to Science Signaling