Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres
- University of Reading, United Kingdom
- Hull York Medical School, United Kingdom
- Manchester Metropolitan University, United Kingdom
- Lithuanian Sports University, Lithuania
- University Medical Center Freiburg, Germany
- University of Freiburg, Germany
- University of Oslo, Norway
- Kristiania University College, Norway
- University of Padua, Italy
- Haartman Institute, University of Helsinki, Finland
- University of Health Science Center, Texas
- Albert-Ludwigs-University Freiburg, Texas
- FRIAS, Freiburg Institute for Advanced Studies and Center for Biological System Analysis ZBSA, Germany
Figures
Figure 1 with 1 supplement
Concomitant skeletal muscle hypertrophy and tissue specific expression of ERRγ and resultant fatigue resistant characteristics.
(A) ERRγ mRNA levels. (B) Body and (C–F) skeletal muscle mass in wild type (Wt), myostatin null (Mtn) and ERRγ transgenic mice on the myostatin null background (Mtn:Eγ). (G) Exercise tolerance test …
Figure 1—figure supplement 1
Contractile properties of the soleus.
(A) Contractile properties of the Soleus. N = 3 male twelve-week old mice per group; One-way ANOVA followed by Bonferroni's multiple comparison tests, *p<0.05
Figure 2 with 1 supplement
Musclespecific expression of ERRγ maintain the hyperplasia in the myostatin null background and normalizes myosin type II phenotype.
(A) Representative immunohistochemical images for MHC IIA and IIB staining in the EDL muscle. (B) EDL total fibre number and myofibre cross sectional area (CSA, μm2). (C) EDL, soleus and superficial …
Figure 2—figure supplement 1
Reprogramming of the soleus myostatin null muscle by ERRγ.
(A) Representative immunohistochemical images for MHC I (red) and IIA (green) staining in the soleus muscle. (B) Soleus total fibre number and MHC myofibre cross sectional area (CSA, μm2). N = 5 …
Figure 3 with 1 supplement
Musclespecific expression of ERRγ normalizes the metabolic and capillary profile of myostatin null mice.
(A) SDH staining and quantification of EDL and soleus muscles of Wt, Mtn and Mtn:Eγ mice. N = 5 male twelve-week old mice per group; One-way ANOVA followed by Bonferroni's multiple comparison tests, …
Figure 3—figure supplement 1
Reprogramming of the tibialis anterior muscle of myostatin null mice by ERRγ.
(A) Representative immunohistochemical images for MHC IIB (red) and IIA (green) staining in deep and superficial regions of the TA muscle. (B) SDH staining of the deep TA muscle. (C) MHC myofibre …
Figure 4
Molecular reprogramming of myostatin null muscle by ERRγ and its ability to promote capillary formation by the expression of angiogenic factors.
(A) Gene expression levels of transcriptional regulators, glucose metabolism regulators, oxidative metabolism genes, antioxidant and oxygen handling genes and fat metabolism genes. (B) Angiogenic …
Figure 5
Musclespecific expression of ERRγ normalizes ultra-structural abnormalities myostatin null mice.
(A) Transmission electron microscopy images in longitudinal and transverse sections of WT, Mtn and Mtn:Eγ muscle, scale 0.5 μm. Note the large spaces (red arrow) disrupted Z-lines (red arrowhead) …
Figure 6
Oxidative muscle developed through ERRγ in the muscle of myostatin null mice shows depletion of satellite cells and increased myonuclie content.
(A) Single EDL muscle fibres stained with DAPI to visualize myonuclei. (B) Quantification of myonuclear number in EDL fibres. (C) Quiescent satellite cells stained for Pax7 on freshly isolated (T = 0…
Figure 7 with 1 supplement
Skeletal muscle regeneration is accelerated by the expression of Errγ in myostatin null mice through enhanced macrophage and satellite cell activity.
Skeletal muscle regeneration in response to cardiotoxin injury. (A) Muscle necrotic fibres visualized by IgG staining at Day 3 (arrows). (B) Quantification of dying fibre size at Day 3. (C) …
Figure 7—figure supplement 1
Characterisation of regenerating tibialis anterior muscle at day 14.
(A) Abundance of eMHC fibres in CTX damaged TA after 14 days. (B) Cross sectional area of regenerating centrally locating nuclei containing fibres in damaged TA after 14 days. N = 3 male twelve-week …
Figure 8 with 1 supplement
Post-natal inhibition of myostatin in the muscle-specific ERRγ mice leads to hypertrophic muscle with enhanced oxidative and vascular features.
(A) Body mass in 12-week-old mice after an 8 week treatment regime. (B) EDL muscle mass after sACtRIIB treatment. (C) Muscle fibre type profiling with MHCIIA (green) and MHCIIB (red) antibodies. (D) …
Figure 8—figure supplement 1
Muscle characterisation after post-natal inhibition of myostatin in the muscle specific ERRγ mice.
(A) Quantification of muscle mass in the Tibialis anterior (TA), gastrocnemius and soleus muscle. (B) Profiling of EDL CSA based on MHC isoforms in WT and Errγ after sActRIIB treatment. Note the …
Additional files
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Supplementary file 1
List of primary and secondary antibodies and qPCR primer sequences.
- https://doi.org/10.7554/eLife.16940.015
