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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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MHC isoforms and ATPase activity in 4- and 12-wk-old  mice. (A) Electrophoretic separation of MHC isoforms of muscles from soleus, diaphragm, and gastrocnemius. Four major isoforms (IIX/D, IIA, IIB, and I) can be identified. When we compared the desmin +/+, +/−, and −/− mice, similar patterns were  found at 4 wk. However, the yield of MHC per mg of tissue was  always much less in the Des −/− mice. Note the decreased  amount of IIA and IIX MHC in the soleus, and IIB in the diaphragm (at 12 wk). (B) Quantification of the number of slow and  fast fibers present in three muscles by ATPase activity at 4 and 12  wk. Slow fibers, such as type I (black), exhibit a high activity,  whereas fast fibers, such as type II (white), display a low ATPase  activity after acid preincubation. Percentage of fast and slow fibers was measured in the soleus, diaphragm, and gastrocnemius  of Des +/+ and −/− mice. In the soleus of Des −/− at 12 wk,  note a decrease of fast fibers (white bar) corresponding to the disappearance of the type IIA and X MHC. A relative increase in  the percentage of slow fibers (black) was found.
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Figure 4: MHC isoforms and ATPase activity in 4- and 12-wk-old mice. (A) Electrophoretic separation of MHC isoforms of muscles from soleus, diaphragm, and gastrocnemius. Four major isoforms (IIX/D, IIA, IIB, and I) can be identified. When we compared the desmin +/+, +/−, and −/− mice, similar patterns were found at 4 wk. However, the yield of MHC per mg of tissue was always much less in the Des −/− mice. Note the decreased amount of IIA and IIX MHC in the soleus, and IIB in the diaphragm (at 12 wk). (B) Quantification of the number of slow and fast fibers present in three muscles by ATPase activity at 4 and 12 wk. Slow fibers, such as type I (black), exhibit a high activity, whereas fast fibers, such as type II (white), display a low ATPase activity after acid preincubation. Percentage of fast and slow fibers was measured in the soleus, diaphragm, and gastrocnemius of Des +/+ and −/− mice. In the soleus of Des −/− at 12 wk, note a decrease of fast fibers (white bar) corresponding to the disappearance of the type IIA and X MHC. A relative increase in the percentage of slow fibers (black) was found.

Mentions: To determine the pattern of muscle fiber type formation we have analyzed the different myosin isoforms by gel electrophoresis. Experiments were carried out on 1- and 3-mo-old mice. Three muscles were chosen: the diaphragm, a continually active muscle even before birth; the soleus, a postural and weight-bearing muscle; and the gastrocnemius, a typical fast-phasic muscle. Electrophoretic separation of MHC isoforms from these muscles is shown Fig. 4 A. Four major isoforms (IIx/D, IIA, IIB, and I) were identified in these muscles. When we compared the Des +/+ and −/− mice, similar patterns of MHC were found at 1 and 3 mo. However, the yield of MHCs per mg of tissue was always less in the Des −/− mice (15–20%).


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)

MHC isoforms and ATPase activity in 4- and 12-wk-old  mice. (A) Electrophoretic separation of MHC isoforms of muscles from soleus, diaphragm, and gastrocnemius. Four major isoforms (IIX/D, IIA, IIB, and I) can be identified. When we compared the desmin +/+, +/−, and −/− mice, similar patterns were  found at 4 wk. However, the yield of MHC per mg of tissue was  always much less in the Des −/− mice. Note the decreased  amount of IIA and IIX MHC in the soleus, and IIB in the diaphragm (at 12 wk). (B) Quantification of the number of slow and  fast fibers present in three muscles by ATPase activity at 4 and 12  wk. Slow fibers, such as type I (black), exhibit a high activity,  whereas fast fibers, such as type II (white), display a low ATPase  activity after acid preincubation. Percentage of fast and slow fibers was measured in the soleus, diaphragm, and gastrocnemius  of Des +/+ and −/− mice. In the soleus of Des −/− at 12 wk,  note a decrease of fast fibers (white bar) corresponding to the disappearance of the type IIA and X MHC. A relative increase in  the percentage of slow fibers (black) was found.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: MHC isoforms and ATPase activity in 4- and 12-wk-old mice. (A) Electrophoretic separation of MHC isoforms of muscles from soleus, diaphragm, and gastrocnemius. Four major isoforms (IIX/D, IIA, IIB, and I) can be identified. When we compared the desmin +/+, +/−, and −/− mice, similar patterns were found at 4 wk. However, the yield of MHC per mg of tissue was always much less in the Des −/− mice. Note the decreased amount of IIA and IIX MHC in the soleus, and IIB in the diaphragm (at 12 wk). (B) Quantification of the number of slow and fast fibers present in three muscles by ATPase activity at 4 and 12 wk. Slow fibers, such as type I (black), exhibit a high activity, whereas fast fibers, such as type II (white), display a low ATPase activity after acid preincubation. Percentage of fast and slow fibers was measured in the soleus, diaphragm, and gastrocnemius of Des +/+ and −/− mice. In the soleus of Des −/− at 12 wk, note a decrease of fast fibers (white bar) corresponding to the disappearance of the type IIA and X MHC. A relative increase in the percentage of slow fibers (black) was found.
Mentions: To determine the pattern of muscle fiber type formation we have analyzed the different myosin isoforms by gel electrophoresis. Experiments were carried out on 1- and 3-mo-old mice. Three muscles were chosen: the diaphragm, a continually active muscle even before birth; the soleus, a postural and weight-bearing muscle; and the gastrocnemius, a typical fast-phasic muscle. Electrophoretic separation of MHC isoforms from these muscles is shown Fig. 4 A. Four major isoforms (IIx/D, IIA, IIB, and I) were identified in these muscles. When we compared the Des +/+ and −/− mice, similar patterns of MHC were found at 1 and 3 mo. However, the yield of MHCs per mg of tissue was always less in the Des −/− mice (15–20%).

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