Building Muscle-TRIM32

What causes Muscular Dystrophies like Limb girdle muscular dystrophy type 2H (LGMD2H)? Here researchers demonstrate for the first time that TRIM32 is expressed in the skeletal muscle stem cell lineage of adult mice, and that in the absence of TRIM32, myogenic differentiation is disrupted. Moreover, they show that the ubiquitin ligase TRIM32 controls this process through the regulation of c-Myc, a similar mechanism to that previously observed in neural progenitors. Importantly, they show that loss of TRIM32 function induces a LGMD2H-like phenotype and strongly affects muscle regeneration in vivo. These studies implicate that the loss of TRIM32 results in dysfunctional muscle stem cells which could contribute to the development of LGMD2H: Nicklas S , Otto A , Wu X , Miller P , Stelzer S , et al. 2012 TRIM32 Regulates Skeletal Muscle Stem Cell Differentiation and Is Necessary for Normal Adult Muscle Regeneration. PLoS ONE 7(1): e30445. doi:10.1371/journal.pone.0030445.

Stem Cell Markers  like PAX7 are important for types of studies. PAX7 is a marker for muscle progenitors or stem cells. If these cells fail to differentiate the level of PAX7 expression will remain high. MyoD is an indicator for successfully differentiating cells. As a consequence, MyoD expression levels increase within the cell and the ratio of Pax7:MyoD is reduced, thus inhibiting proliferation and inducing differentiation through Myogenin expression. In the absence of TRIM32, this balance of Pax7:MyoD is dysregulated, because degradation of c-Myc is not initiated, MyoD levels do not increase and Myogenin expression is not activated.

Figure . Differentiation is strongly reduced in satellite cell progeny on TRIM32−/− myofibers. (a), (c) and (e) Immunostainings of satellite cells on freshly isolated myofibers from wild type (+/+) and TRIM32−/− (−/−) mice cultured for 24 h (a), 48 h (c) and 72 h (e) and labelled with the indicated markers (upper grey boxes). (b), (d) and (f) Diagrams showing the relative frequency of Pax7+/MyoD− cells on fibers cultured for 24 h (b), Pax7+/Myogenin− cells on fibers cultured for 48 h (d) and Pax7−/Myogenin+ cells on fibers cultured for 72 h (f). In all cases cells on myofibers from wild type mice and TRIM32−/− mice are compared. (mean ± std; *P<0.001 compared to wild type).


Check out our more publications referencing use of our PAX7.