Muscular dystrophy in PTFR/cavin-1 null mice
Shi-Ying Ding, Libin Liu, Paul F. Pilch
Shi-Ying Ding, Libin Liu, Paul F. Pilch
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Research Article Cell biology Muscle biology

Muscular dystrophy in PTFR/cavin-1 null mice

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 3

Cavin-1 null mice display elevated levels of dystrophin-glycoprotein complex (DGC) components, membrane repair proteins, and T-tubule–system components, accompanied with impaired sarcolemmal protein distribution and membrane integrity.

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Cavin-1 null mice display elevated levels of dystrophin-glycoprotein com...
(A) Representative Western blot analysis of muscular dystrophy–related proteins. Muscle extracts from 12-week-old WT and KO mice were immunoblotted with the indicated antibodies. Cav3, caveolin-3; α-Sarcoglycan and β-dystroglycan are components of the DGC; dihydropyridine receptor (DHPRα2) is a marker of T-tubules; ryanodine receptor (RyR1) is a marker of the junctional sarcoplasmic reticulum; MG53 and dysferlin are membrane repair proteins; α-tubulin, vimentin and α-actin are involved in the cytoskeleton network. The experiment was replicated 3 times. (B) Dystrophin and β-dystroglycan immunofluorescence histochemistry (dystrophin and β-dystroglycan, red; laminin, green) on 8-μm cryosections of soleus muscle from 12-week-old WT and cavin-1 KO mice. Nuclei were stained with DAPI. Insets show increased intracellular immunofluorescence of dystrophin and β-dystroglycan in KO mice. Scale bars: 100 μm. (C) Serum creatine kinase (CK) levels in WT and cavin-1 KO mice (n = 5–6). Data are represented as mean ± SEM. Two-tailed Student’s t test was used for comparison between WT and KO mice. *P < 0.05.