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Muscular dystrophy in PTFR/cavin-1 null mice
Shi-Ying Ding, … , Libin Liu, Paul F. Pilch
Shi-Ying Ding, … , Libin Liu, Paul F. Pilch
Published March 9, 2017
Citation Information: JCI Insight. 2017;2(5):e91023. https://doi.org/10.1172/jci.insight.91023.
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Research Article Cell biology Muscle biology

Muscular dystrophy in PTFR/cavin-1 null mice

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Abstract

Mice and humans lacking the caveolae component polymerase I transcription release factor (PTRF, also known as cavin-1) exhibit lipo- and muscular dystrophy. Here we describe the molecular features underlying the muscle phenotype for PTRF/cavin-1 null mice. These animals had a decreased ability to exercise, and exhibited muscle hypertrophy with increased muscle fiber size and muscle mass due, in part, to constitutive activation of the Akt pathway. Their muscles were fibrotic and exhibited impaired membrane integrity accompanied by an apparent compensatory activation of the dystrophin-glycoprotein complex along with elevated expression of proteins involved in muscle repair function. Ptrf deletion also caused decreased mitochondrial function, oxygen consumption, and altered myofiber composition. Thus, in addition to compromised adipocyte-related physiology, the absence of PTRF/cavin-1 in mice caused a unique form of muscular dystrophy with a phenotype similar or identical to that seen in humans lacking this protein. Further understanding of this muscular dystrophy model will provide information relevant to the human situation and guidance for potential therapies.

Authors

Shi-Ying Ding, Libin Liu, Paul F. Pilch

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Figure 6

Cavin-1 KO mice exhibit alteration of skeletal muscle fiber type.

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Cavin-1 KO mice exhibit alteration of skeletal muscle fiber type.
(A) mR...
(A) mRNA expression of myosin heavy chain (MHC) isoforms in gastrocnemius/plantaris (G/P) muscle, determined by quantitative real-time PCR (n = 6). (B) mRNA expression of MHC isoforms in soleus muscle (n = 6). (C) Representative immunofluorescence histochemistry using NOQ7.5.4D anti–MHC-I antibody on soleus muscle cryosections of WT and cavin-1 KO mice. Nuclei are stained with DAPI. Scale bars: 100 μm. Quantitative analysis of percentage of MHC-I–positive fibers (red) is shown in the bottom panel (n = 4), by using ImageJ software to count the number of total and positively stained myofibers. (D) Representative metachromatic ATPase staining on soleus muscle cryosections and quantitative analysis of type I fiber (dark blue) percentage (n = 6). Scale bars: 50 μm. Data are represented as mean ± SEM. Bonferroni’s multiple comparison test (A and B) or 2-tailed Student’s t test (C and D) were used to determine the statistical significance. *P < 0.05; ***P < 0.001.

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