What is the clinical evidence from this study?

Study design: Other. Population: Muscle hypertrophy (n=6). Intervention: Synergist-ablation mechanical overload (MOV) vs. SHAM surgery. Primary outcome: Resident myonuclear (RMN) volume (p=<0.05).

What does this research mean for the field?

Mechanical overload for 72 hours increases resident myonuclear volume and myonuclear domain size in single muscle fibers. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aimed to quantify changes in myonuclear content and organization in muscle fibers under mechanical overload compared to control conditions.

May 14, 2026

Resident myonuclear adaptations to mechanical overload in single muscle fibers of HSA-GFP mice

Q: What are the key findings of this study?

Mechanical overload for 72 hours in HSA-GFP mice increased resident myonuclear volume by 11.5% (p<0.05) and myonuclear domain size by 37.8% (p<0.05) compared to SHAM surgery.

Q: What does this research mean for the field?

Mechanical overload for 72 hours increases resident myonuclear volume and myonuclear domain size in single muscle fibers. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

This research aimed to quantify changes in myonuclear content and organization in muscle fibers under mechanical overload compared to control conditions.

Key Result

Mechanical overload for 72 hours in HSA-GFP mice increased resident myonuclear volume by 11.5% (p<0.05) and myonuclear domain size by 37.8% (p<0.05) compared to SHAM surgery.

Key Points

This research aimed to quantify changes in myonuclear content and organization in muscle fibers under mechanical overload compared to control conditions.
Used HSA-GFP mouse model for fluorescence labeling of myonuclei
Conducted surgical intervention for mechanical overload (MOV) and SHAM control
Analyzed muscle fiber samples using 3D imaging and statistical methods for various nuclear metrics.
RMN volume increased by 11.5% in MOV fibers (1.62×10⁶ µm³) versus SHAM (1.46×10⁶ µm³; p<0.05)
MND was 37.8% larger in MOV (8.88×10⁴ µm³) compared to SHAM (6.44×10⁴ µm³; p<0.05)
NND was 12.9% greater in MOV (35±6 µm) compared to SHAM (31±4 µm; p<0.05).

Structured PICO

Does mechanical overload alter myonuclear volume, domain size, and spatial organization in single muscle fibers of HSA-GFP mice?

Population

Young HSA-GFP mice (10-12 weeks of age), n=6

Intervention

Synergist-ablation mechanical overload (MOV) model for 72 hours

Comparator

SHAM surgery

Outcome

Myonuclear content, morphology (shape), and spatial organization (volume, myonuclear domain, nearest-neighbor distance, shape, clustering, and nucleolar morphology) in GFP-labeled resident myonuclei from isolated single muscle fiberssurrogate

Mechanical overload induces rapid structural adaptations in resident myonuclei within 72 hours, including increased volume and myonuclear domain size.

Main Result

Absolute Event Rate: 1620000% vs 1460000%

p-value: p=<0.05

Abstract

Myonuclear number, morphology, and spatial organization change during muscle growth and repair, but the structural adaptations of resident myonuclei (RMN) within single muscle fibers (SMF) under hypertrophic stimuli remain poorly understood. The HSA-GFP mouse model allows direct identification of RMN within intact SMF, enabling assessment of RMN-specific nuclear responses to acute hypertrophic stimulus using the synergist-ablation mechanical overload (MOV) model. Objective: We aimed to quantify myonuclear content, morphology (shape), and spatial organization in GFP-labeled RMN from isolated SMF under MOV versus control (SHAM) conditions. We hypothesized that MOV would increase myonuclear domain (MND) size and RMN volume and alter nuclear spacing and organization versus SHAM fibers. Methods: RMN from young mice (10-12 wks of age) were fluorescently labeled with GFP prior to experimentation using a muscle fiber-specific doxycycline-inducible recombination-independent mouse model called HSA-GFP. Plantaris muscles from six HSA-GFP mice were collected after 72 h MOV or SHAM surgery (n=3 per group). Paraformaldehyde fixed SMF were isolated and imaged in three-dimensions (3D) via laser-scanning confocal microscopy (Leica Stellaris 5), and GFP-labeled nuclei were analyzed for volume, MND, nearest-neighbor distance (NND), shape, clustering, and nucleolar morphology using ImageJ (FIJI) and SPSS. The threshold for significance was set at p ≤ 0.05. Results: A total of 120 SMF and 2,501 RMN were 3D imaged and analyzed. Following 72 h MOV, GFP-labeled RMN volume was 11.5% greater in MOV fibers (1.62×10 6 ± 5.07×10 5 µm³) versus SHAM (1.46×10 6 ± 3.25×10 5 µm³; p < 0.05). MND was 37.8% larger in MOV (8.88×10 4 ± 3.55×10 4 µm³) versus SHAM (6.44×10 4 ± 2.13×10 4 µm³; p < 0.05). NND was 12.9% greater in MOV (35±6 µm) versus SHAM (31±4 µm; p < 0.05). Relative nucleolar volume was smaller in MOV fibers versus SHAM (p < 0.05). Nuclear shape and clustering did not significantly differ between groups after the 72 h stimulus. Conclusion: The HSA-GFP model distinguished resident from total nuclei in SMF and revealed early (72 h) structural RMN adaptations after MOV. Increased RMN volume, larger MND, and altered nuclear spacing highlight rapid resident nuclear remodeling that may inform future studies on muscle adaptation in aging, unloading, disease, and regeneration. Funding: NIH AG063994 to KAM; CSUBIOTECH grant to JRB. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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