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Desmin is essential for the tensile strength and integrity of myofibrils but not for myogenic commitment, differentiation, and fusion of skeletal muscle.

Li Z, Mericskay M, Agbulut O, Butler-Browne G, Carlsson L, Thornell LE, Babinet C, Paulin D - J. Cell Biol. (1997)

Bottom Line: Our results demonstrate that all early stages of muscle differentiation and cell fusion occur normally.However, myofibrillogenesis in regenerating fibers is often abortive, indicating that desmin may be implicated in this repair process.The results presented here show that desmin is essential to maintain the structural integrity of highly solicited skeletal muscle.

View Article: PubMed Central - PubMed

Affiliation: Station Centrale de Microscopie Electronique, Institut Pasteur, Paris, France.

ABSTRACT
A mutation was introduced into the mouse desmin gene by homologous recombination. The desmin knockout mice (Des -/-) develop normally and are fertile. However, defects were observed after birth in skeletal, smooth, and cardiac muscles (Li, Z., E. Colucci-Guyon, M. Pincon-Raymond, M. Mericskay, S. Pournin, D. Paulin, and C. Babinet. 1996. Dev. Biol. 175:362-366; Milner, D.J., G. Weitzer, D. Tran, A. Bradley, and Y. Capetanaki. 1996. J. Cell Biol. 134:1255- 1270). In the present study we have carried out a detailed analysis of somitogenesis, muscle formation, maturation, degeneration, and regeneration in Des -/- mice. Our results demonstrate that all early stages of muscle differentiation and cell fusion occur normally. However, after birth, modifications were observed essentially in weight-bearing muscles such as the soleus or continually used muscles such as the diaphragm and the heart. In the absence of desmin, mice were weaker and fatigued more easily. The lack of desmin renders these fibers more susceptible to damage during contraction. We observed a process of degeneration of myofibers, accompanied by macrophage infiltration, and followed by a process of regeneration. These cycles of degeneration and regeneration resulted in a relative increase in slow myosin heavy chain (MHC) and decrease in fast MHC. Interestingly, this second wave of myofibrillogenesis during regeneration was often aberrant and showed signs of disorganization. Subsarcolemmal accumulation of mitochondria were also observed in these muscles. The lack of desmin was not compensated by an upregulation of vimentin in these mice either during development or regeneration. Absence of desmin filaments within the sarcomere does not interfere with primary muscle formation or regeneration. However, myofibrillogenesis in regenerating fibers is often abortive, indicating that desmin may be implicated in this repair process. The results presented here show that desmin is essential to maintain the structural integrity of highly solicited skeletal muscle.

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Transmission electron microscopy of myofibers  of soleus from Des −/−  2-wk-old mouse. (A) Cross  section of 2-wk soleus showing an area of a normal dense  myofibrillar pattern and an  area containing several small-size cells. c, capillaries. (B) In  higher magnification, the  small-size cells are identified  as macrophages (m) with well-organized rough endoplasmic  reticulum. Activated satellite cells having light cytoplasm with dispersed ribosomes (*). All these cells are  enclosed by the same basement membrane (arrows).  (C) Longitudinal sections of  muscle fiber, one with light  cytoplasm, runs in parallel  with two other well-organized  myofibrils. (D) Higher magnification view of the boxed  area in C, showing disorganized myofibrils (mf) and the  Z bodies (arrows). (E) Higher  magnification view of the encircled area in C, showing an  organized sarcomere with Z  disks and abundant ribosomes  (*). (F) Muscle fiber with areas of light cytoplasm (*) and  many large nuclei (n) containing prominent nucleoli run  parallel to muscle fibers with  well-organized myofibrils.  Bars: (A, C, and E) 5 μm; (B  and D) 1 μm; (E) 0.5 μm.
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Figure 6: Transmission electron microscopy of myofibers of soleus from Des −/− 2-wk-old mouse. (A) Cross section of 2-wk soleus showing an area of a normal dense myofibrillar pattern and an area containing several small-size cells. c, capillaries. (B) In higher magnification, the small-size cells are identified as macrophages (m) with well-organized rough endoplasmic reticulum. Activated satellite cells having light cytoplasm with dispersed ribosomes (*). All these cells are enclosed by the same basement membrane (arrows). (C) Longitudinal sections of muscle fiber, one with light cytoplasm, runs in parallel with two other well-organized myofibrils. (D) Higher magnification view of the boxed area in C, showing disorganized myofibrils (mf) and the Z bodies (arrows). (E) Higher magnification view of the encircled area in C, showing an organized sarcomere with Z disks and abundant ribosomes (*). (F) Muscle fiber with areas of light cytoplasm (*) and many large nuclei (n) containing prominent nucleoli run parallel to muscle fibers with well-organized myofibrils. Bars: (A, C, and E) 5 μm; (B and D) 1 μm; (E) 0.5 μm.

Mentions: Using the electron microscope, we examined more closely the ultrastructure of the soleus, the weight-bearing muscle, from newborn to 10-wk-old mutant mice. From 2 wk and onwards, Des −/− mice show unquestionable signs of muscle fiber death (Fig. 6). Focal areas with the size of a muscle fiber diameter showed macrophage accumulation and presence of cells having characteristics of activated satellite cells, i.e., light cytoplasm with many ribosomes, nascent myofilaments, and large, centrally placed nuclei. Remnants of a surrounding basement membrane were often seen. In other areas in muscles of the same age profiles concurrent with fiber splitting were observed. In longitudinal sections, muscle fibers having a light cytoplasm contained some organized myofibrils, but mainly disorganized myofibrils were observed in all groups after 2 wk of age.


Desmin is essential for the tensile strength and integrity of myofibrils but not for myogenic commitment, differentiation, and fusion of skeletal muscle.

Li Z, Mericskay M, Agbulut O, Butler-Browne G, Carlsson L, Thornell LE, Babinet C, Paulin D - J. Cell Biol. (1997)

Transmission electron microscopy of myofibers  of soleus from Des −/−  2-wk-old mouse. (A) Cross  section of 2-wk soleus showing an area of a normal dense  myofibrillar pattern and an  area containing several small-size cells. c, capillaries. (B) In  higher magnification, the  small-size cells are identified  as macrophages (m) with well-organized rough endoplasmic  reticulum. Activated satellite cells having light cytoplasm with dispersed ribosomes (*). All these cells are  enclosed by the same basement membrane (arrows).  (C) Longitudinal sections of  muscle fiber, one with light  cytoplasm, runs in parallel  with two other well-organized  myofibrils. (D) Higher magnification view of the boxed  area in C, showing disorganized myofibrils (mf) and the  Z bodies (arrows). (E) Higher  magnification view of the encircled area in C, showing an  organized sarcomere with Z  disks and abundant ribosomes  (*). (F) Muscle fiber with areas of light cytoplasm (*) and  many large nuclei (n) containing prominent nucleoli run  parallel to muscle fibers with  well-organized myofibrils.  Bars: (A, C, and E) 5 μm; (B  and D) 1 μm; (E) 0.5 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139820&req=5

Figure 6: Transmission electron microscopy of myofibers of soleus from Des −/− 2-wk-old mouse. (A) Cross section of 2-wk soleus showing an area of a normal dense myofibrillar pattern and an area containing several small-size cells. c, capillaries. (B) In higher magnification, the small-size cells are identified as macrophages (m) with well-organized rough endoplasmic reticulum. Activated satellite cells having light cytoplasm with dispersed ribosomes (*). All these cells are enclosed by the same basement membrane (arrows). (C) Longitudinal sections of muscle fiber, one with light cytoplasm, runs in parallel with two other well-organized myofibrils. (D) Higher magnification view of the boxed area in C, showing disorganized myofibrils (mf) and the Z bodies (arrows). (E) Higher magnification view of the encircled area in C, showing an organized sarcomere with Z disks and abundant ribosomes (*). (F) Muscle fiber with areas of light cytoplasm (*) and many large nuclei (n) containing prominent nucleoli run parallel to muscle fibers with well-organized myofibrils. Bars: (A, C, and E) 5 μm; (B and D) 1 μm; (E) 0.5 μm.
Mentions: Using the electron microscope, we examined more closely the ultrastructure of the soleus, the weight-bearing muscle, from newborn to 10-wk-old mutant mice. From 2 wk and onwards, Des −/− mice show unquestionable signs of muscle fiber death (Fig. 6). Focal areas with the size of a muscle fiber diameter showed macrophage accumulation and presence of cells having characteristics of activated satellite cells, i.e., light cytoplasm with many ribosomes, nascent myofilaments, and large, centrally placed nuclei. Remnants of a surrounding basement membrane were often seen. In other areas in muscles of the same age profiles concurrent with fiber splitting were observed. In longitudinal sections, muscle fibers having a light cytoplasm contained some organized myofibrils, but mainly disorganized myofibrils were observed in all groups after 2 wk of age.

Bottom Line: Our results demonstrate that all early stages of muscle differentiation and cell fusion occur normally.However, myofibrillogenesis in regenerating fibers is often abortive, indicating that desmin may be implicated in this repair process.The results presented here show that desmin is essential to maintain the structural integrity of highly solicited skeletal muscle.

View Article: PubMed Central - PubMed

Affiliation: Station Centrale de Microscopie Electronique, Institut Pasteur, Paris, France.

ABSTRACT
A mutation was introduced into the mouse desmin gene by homologous recombination. The desmin knockout mice (Des -/-) develop normally and are fertile. However, defects were observed after birth in skeletal, smooth, and cardiac muscles (Li, Z., E. Colucci-Guyon, M. Pincon-Raymond, M. Mericskay, S. Pournin, D. Paulin, and C. Babinet. 1996. Dev. Biol. 175:362-366; Milner, D.J., G. Weitzer, D. Tran, A. Bradley, and Y. Capetanaki. 1996. J. Cell Biol. 134:1255- 1270). In the present study we have carried out a detailed analysis of somitogenesis, muscle formation, maturation, degeneration, and regeneration in Des -/- mice. Our results demonstrate that all early stages of muscle differentiation and cell fusion occur normally. However, after birth, modifications were observed essentially in weight-bearing muscles such as the soleus or continually used muscles such as the diaphragm and the heart. In the absence of desmin, mice were weaker and fatigued more easily. The lack of desmin renders these fibers more susceptible to damage during contraction. We observed a process of degeneration of myofibers, accompanied by macrophage infiltration, and followed by a process of regeneration. These cycles of degeneration and regeneration resulted in a relative increase in slow myosin heavy chain (MHC) and decrease in fast MHC. Interestingly, this second wave of myofibrillogenesis during regeneration was often aberrant and showed signs of disorganization. Subsarcolemmal accumulation of mitochondria were also observed in these muscles. The lack of desmin was not compensated by an upregulation of vimentin in these mice either during development or regeneration. Absence of desmin filaments within the sarcomere does not interfere with primary muscle formation or regeneration. However, myofibrillogenesis in regenerating fibers is often abortive, indicating that desmin may be implicated in this repair process. The results presented here show that desmin is essential to maintain the structural integrity of highly solicited skeletal muscle.

Show MeSH
Related in: MedlinePlus