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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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Detection of myosin isoforms, desmin and  vimentin, by immunofluorescence in fetuses and in 1-mo-old mice. Mutant Des −/−  (B, D, F, H, J, and L) and  control Des +/+ (A, C, E, G,  I, and K). (A–D) Characterization of primary and secondary generation muscle  fibers at 17.5 d.p.c. Immunofluorescent staining of anterior shoulder muscles on  transverse sections of the  subscapularis muscle with  antibody against slow MHC,  which labels primary muscle  fibers (A and B) and using an  antibody against MHC,  which labels secondary muscle fibers (C and D). The  same pattern was found in  Des +/+ and Des −/− fetuses. (E–H) Detection of  desmin using a polyclonal antidesmin antibody showed a  typical reactivity in Des +/+  in 17.5-d.p.c. fetuses (E) and  1-mo-old mice (G). No reactivity was found in Des −/−  fetus (F) or 1-mo-old mice  (H). (I–L) Detection of vimentin using polyclonal anti-vimentin antibody performed on 17.5-d.p.c. fetuses  (I and J) and 1-mo-old mice  (K and L). The same pattern  was found in Des +/+ and  Des −/− mice. No vimentin  reactivity was found inside  the myofibers. The vimentin  reactivity found around the  myofibers corresponded to  connective tissue forming the  endomysium and the mesenchymal cells of vessels. Bars:  (A–F) 25 μm; (I and J) 25  μm; (G, H, K, and L) 50 μm.
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Figure 3: Detection of myosin isoforms, desmin and vimentin, by immunofluorescence in fetuses and in 1-mo-old mice. Mutant Des −/− (B, D, F, H, J, and L) and control Des +/+ (A, C, E, G, I, and K). (A–D) Characterization of primary and secondary generation muscle fibers at 17.5 d.p.c. Immunofluorescent staining of anterior shoulder muscles on transverse sections of the subscapularis muscle with antibody against slow MHC, which labels primary muscle fibers (A and B) and using an antibody against MHC, which labels secondary muscle fibers (C and D). The same pattern was found in Des +/+ and Des −/− fetuses. (E–H) Detection of desmin using a polyclonal antidesmin antibody showed a typical reactivity in Des +/+ in 17.5-d.p.c. fetuses (E) and 1-mo-old mice (G). No reactivity was found in Des −/− fetus (F) or 1-mo-old mice (H). (I–L) Detection of vimentin using polyclonal anti-vimentin antibody performed on 17.5-d.p.c. fetuses (I and J) and 1-mo-old mice (K and L). The same pattern was found in Des +/+ and Des −/− mice. No vimentin reactivity was found inside the myofibers. The vimentin reactivity found around the myofibers corresponded to connective tissue forming the endomysium and the mesenchymal cells of vessels. Bars: (A–F) 25 μm; (I and J) 25 μm; (G, H, K, and L) 50 μm.

Mentions: Two major waves of muscle formation lead to primary and secondary generation fibers that display different MHC profiles. To determine the stage of maturation of myofibers, MHC profiles were characterized using antibodies against slow and fast MHC on frozen transversal sections of 17.5-d embryos. Fig. 3, A and B, shows the same positive reaction with the slow MHC antibody in the primary fibers of the trapezius muscles in both Des −/− and Des +/+ mice. Fig. 3, C and D, show the same positive reaction in the secondary fibers of muscles in Des −/−, compared to Des +/+ mice. Thus the absence of desmin does not prevent the fusion of myoblasts, nor the formation and further maturation of myofibers. Since we show that skeletal muscles form normally in the Des −/− mice, it is reasonable to propose that in vivo desmin is not essential for myogenic commitment, myoblast fusion, or differentiation.


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)

Detection of myosin isoforms, desmin and  vimentin, by immunofluorescence in fetuses and in 1-mo-old mice. Mutant Des −/−  (B, D, F, H, J, and L) and  control Des +/+ (A, C, E, G,  I, and K). (A–D) Characterization of primary and secondary generation muscle  fibers at 17.5 d.p.c. Immunofluorescent staining of anterior shoulder muscles on  transverse sections of the  subscapularis muscle with  antibody against slow MHC,  which labels primary muscle  fibers (A and B) and using an  antibody against MHC,  which labels secondary muscle fibers (C and D). The  same pattern was found in  Des +/+ and Des −/− fetuses. (E–H) Detection of  desmin using a polyclonal antidesmin antibody showed a  typical reactivity in Des +/+  in 17.5-d.p.c. fetuses (E) and  1-mo-old mice (G). No reactivity was found in Des −/−  fetus (F) or 1-mo-old mice  (H). (I–L) Detection of vimentin using polyclonal anti-vimentin antibody performed on 17.5-d.p.c. fetuses  (I and J) and 1-mo-old mice  (K and L). The same pattern  was found in Des +/+ and  Des −/− mice. No vimentin  reactivity was found inside  the myofibers. The vimentin  reactivity found around the  myofibers corresponded to  connective tissue forming the  endomysium and the mesenchymal cells of vessels. Bars:  (A–F) 25 μm; (I and J) 25  μm; (G, H, K, and L) 50 μm.
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Figure 3: Detection of myosin isoforms, desmin and vimentin, by immunofluorescence in fetuses and in 1-mo-old mice. Mutant Des −/− (B, D, F, H, J, and L) and control Des +/+ (A, C, E, G, I, and K). (A–D) Characterization of primary and secondary generation muscle fibers at 17.5 d.p.c. Immunofluorescent staining of anterior shoulder muscles on transverse sections of the subscapularis muscle with antibody against slow MHC, which labels primary muscle fibers (A and B) and using an antibody against MHC, which labels secondary muscle fibers (C and D). The same pattern was found in Des +/+ and Des −/− fetuses. (E–H) Detection of desmin using a polyclonal antidesmin antibody showed a typical reactivity in Des +/+ in 17.5-d.p.c. fetuses (E) and 1-mo-old mice (G). No reactivity was found in Des −/− fetus (F) or 1-mo-old mice (H). (I–L) Detection of vimentin using polyclonal anti-vimentin antibody performed on 17.5-d.p.c. fetuses (I and J) and 1-mo-old mice (K and L). The same pattern was found in Des +/+ and Des −/− mice. No vimentin reactivity was found inside the myofibers. The vimentin reactivity found around the myofibers corresponded to connective tissue forming the endomysium and the mesenchymal cells of vessels. Bars: (A–F) 25 μm; (I and J) 25 μm; (G, H, K, and L) 50 μm.
Mentions: Two major waves of muscle formation lead to primary and secondary generation fibers that display different MHC profiles. To determine the stage of maturation of myofibers, MHC profiles were characterized using antibodies against slow and fast MHC on frozen transversal sections of 17.5-d embryos. Fig. 3, A and B, shows the same positive reaction with the slow MHC antibody in the primary fibers of the trapezius muscles in both Des −/− and Des +/+ mice. Fig. 3, C and D, show the same positive reaction in the secondary fibers of muscles in Des −/−, compared to Des +/+ mice. Thus the absence of desmin does not prevent the fusion of myoblasts, nor the formation and further maturation of myofibers. Since we show that skeletal muscles form normally in the Des −/− mice, it is reasonable to propose that in vivo desmin is not essential for myogenic commitment, myoblast fusion, or differentiation.

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