Key result
Mustn1 knockout in mice alters regenerating muscle fiber types, increasing Type IIa and decreasing IIx/IIb.
Why the study?
To investigate the role of Mustn1 in muscle regeneration using a cardiotoxin-induced tibialis anterior injury model.
Does Mustn1 ablation alter skeletal muscle regeneration and gene expression in male mice?
Does Mustn1 ablation alter skeletal muscle regeneration and gene expression in male mice?
Mustn1 is integral to skeletal muscle fiber composition and myogenic gene expression, facilitating muscle repair and regeneration.
Mustn1 modulates regenerating fiber types in mice; hypothesis-generating for human muscle repair, with no practice implications yet.
We previously developed a Mustn1 conditional knockout (KO) mouse model targeting Pax7‐expressing skeletal muscle satellite cells and showed its role in glucose metabolism, strength, gait, peak contractile strength, and myofiber composition. To investigate Mustn1's role in muscle regeneration, we used these KO mice in a cardiotoxin (CTX)‐induced tibialis anterior injury model. Despite no major histological differences or deficits in ladder climbing between KO and wild‐type (WT) mice at post‐injury (Day 2–10), we observed significant shifts in fiber type composition. Mustn1 KO mice had more Type IIa fibers at Day 5, while Type IIx and IIb fibers were reduced at Day 2 and 10, respectively. Additionally, we observed increases in Type I fiber cross‐sectional area in the Mustn1 KO mice at Day 0 and 2. Lower numbers of centrally nucleated fibers were also seen in the Mustn1 KO mice at Day 10. Pax7 + cells were also greater in numbers in the Mustn1 KO mice at Day 2 and 10. Lastly, expression of myogenic genes also differed significantly between the two strains. These data suggest that Mustn1 is integral to skeletal muscle fiber composition and myogenic gene expression thereby facilitating muscle repair and regeneration.
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Tagliaferri et al. (2026) studied this question. Mustn1 knockout in male mice altered muscle fiber types during regeneration, increasing Type IIa at Day 5, decreasing IIx and IIb, and affecting myogenic gene expression.
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