# Mustn1 ablation in male mice results in fiber type and gene expression alterations during skeletal muscle regeneration

## TL;DR

Removing Mustn1 in male mice changes muscle fiber types and gene activity during muscle repair.

## Contribution

The study reveals Mustn1's role in altering muscle fiber composition and gene expression during regeneration.

## Key findings

- Mustn1 KO mice showed increased Type IIa fibers and decreased Type IIx and IIb fibers during regeneration.
- Mustn1 KO mice had larger Type I fiber cross-sectional area and fewer centrally nucleated fibers at Day 10.
- Pax7+ cell numbers and myogenic gene expression were altered in Mustn1 KO mice.

## Abstract

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.