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.
View: Text | PDF
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

×

Figure 1

Deficiency of cavin-1 results in muscle hypertrophy.

Options: View larger image (or click on image) Download as PowerPoint
Deficiency of cavin-1 results in muscle hypertrophy. (A) Representative ...
(A) Representative pictures of hindlimbs from 12-week-old WT and cavin-1 KO mice. (B) Relative ratio of muscle mass to body weight in WT and KO mice (n = 7–8). (C) Representative H&E staining of tibialis anterior (TA), extensor digitorum longus (EDL), soleus (Sol), and gastrocnemius/plantaris (G/P) muscles of WT and KO mice at 12 weeks of age. Centralized nuclei are indicated with black arrowheads. Scale bars: 50 μm. (D) Analysis of the mean fiber cross-sectional area (CSA) in G/P muscles from 12-week-old WT and KO mice (n = 4, CSA from > 200 myofibers were measured for each mouse). (E) Percentage of centronuclear myofibers in Sol muscles of WT and KO mice at 12 weeks of age (n = 3–5). (F) Immunoblot analysis of caveolae proteins in TA, EDL, Sol, and G/P muscles, and hearts of WT and KO mice (representative of n = 3). Cav1 and Cav3, caveolin-1 and -3. Quantitative analyses are shown in Supplemental Figure 3. Data are represented as mean ± SEM. Two-tailed Student’s t test was used for comparison between WT and KO mice. *P < 0.05, **P < 0.01, ***P < 0.001.