Proteomic analysis of triceps brachii muscle in FLExDUX4 mice

ABSTRACT: FLExDUX4 is an emerging murine experimental model of facioscapulohumeral muscular dystrophy (FSHD) characterized by chronic, low levels of leaky expression of the human full-length double homeobox 4 gene (DUX4-fl). FLExDUX4 mice exhibit age-related declines in muscle size and function similar to the natural history of FSHD progression in human patients. Proteomic studies in FSHD could offer new insights into disease mechanisms underpinned by post-transcriptional processes. We used mass spectrometry-based proteomics to quantify the abundance of 1322 proteins in triceps brachii muscle, encompassing both male and female mice in control and free voluntary wheel running (VWR) in Wild-type (n=3) and FLExDUX4 (n=3) genotypes. We report the triceps brachii proteome of FLExDUX4 mice recapitulates key skeletal muscle clinical characteristics of human FSHD, including alterations to mitochondria, RNA metabolism, oxidative stress, and apoptosis. RNA-binding proteins exhibit a sex-specific difference in FLExDUX4 mice. Sexual dimorphism of mitochondrial protein adaptation to exercise was uncovered specifically in FLExDUX4 mice, where females increased, but males decreased mitochondrial proteins after a 6-week of VWR. Our results highlight the importance of identifying sex-specific diagnostic biomarkers to enable more reliable monitoring of FSHD therapeutic targets. Our data provides a resource for the FSHD research community to explore the burgeoning aspect of sexual dimorphism in FSHD.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skeletal Muscle

DISEASE(S): Facioscapulohumeral Muscular Dystrophy

SUBMITTER: Yusuke Nishimura  

LAB HEAD: Jatin Burniston

PROVIDER: PXD061097 | Pride | 2025-06-09

REPOSITORIES: Pride