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 4

Cavin-1 KO mice show muscle fibrosis and impaired myofiber regeneration.

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Cavin-1 KO mice show muscle fibrosis and impaired myofiber regeneration....
(A) Collagen content in skeletal muscles of WT and KO mice, measured with a Sirius Red Collagen kit (n = 4–6). (B) Representative Masson’s trichrome staining for collagen in muscle sections of WT and KO mice. (C) Quantitative real-time PCR (q-PCR) analysis of mRNA level of fibrosis regulator TGF-β1 in WT and KO muscle (n = 5–7). (D) q-PCR analysis of mRNA levels of collagen genes, as well as genes related to fibrosis such as vimentin (Vim) and fibronectin 1 (Fn1), in WT and KO muscle (n = 5–7). (E) Representative H&E staining on tibialis anterior muscle cryosections of WT and KO mice. Tissues were isolated at days 0, 3, 7, and 14 after cardiotoxin (CTX) injury. Arrows indicate infiltrated adipocytes. The bottom panels show representative Oil Red O (ORO) staining on muscle cryosections of WT and KO mice at 14 days after injury. Scale bars: 50 μm. The experiment was replicated 2 times with 3 or 4 mice per group. Data are represented as mean ± SEM. Two-tailed Student’s t test (A and C) or Bonferroni’s multiple comparison test (D) were used to determine the statistical significance. *P < 0.05; ***P < 0.001.