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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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Analyses of muscular performances on control animal  Des +/+ (white), heterozygous Des +/− (hatched) and homozygous Des −/− (black). (A) The maximum force developed by the  mice was measured by pulling the mouse backwards by the tail  until the bar was released. Animals were allowed to hold the bar  linked to a dynamometer either with all four limbs or with the  two forelimbs. Results are expressed in mN. (B) The maximum  force developed by isolated muscle was measured on soleus from  2- (curve 1: Des +/+; curve 3: Des−/−) and 5-mo-old mice  (curve 2: Des +/+; and curve 4: Des −/−). (C) The muscular endurance was analyzed by measuring the time that animals could  hold onto a 32-g bar, either with all four limbs (4L) or with the  two forelimbs (2L). Results are expressed in s. (D) Motor coordination: performances were measured either by measuring the  time that mice need to cross a rod or by putting the mice on a rotating apparatus. Capacity of Des −/− mice are considerably  modified. (E) CMAP measured in gastrocnemius and plantaris  muscles from 5-mo-old mice. Results are expressed in mV. (F)  Nerve conduction rate measured in gastrocnemius and plantaris  muscles from 5-mo-old mice. The DL is given in ms. Data are the  means ± standard errors computed from each set of experiments.
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Figure 9: Analyses of muscular performances on control animal Des +/+ (white), heterozygous Des +/− (hatched) and homozygous Des −/− (black). (A) The maximum force developed by the mice was measured by pulling the mouse backwards by the tail until the bar was released. Animals were allowed to hold the bar linked to a dynamometer either with all four limbs or with the two forelimbs. Results are expressed in mN. (B) The maximum force developed by isolated muscle was measured on soleus from 2- (curve 1: Des +/+; curve 3: Des−/−) and 5-mo-old mice (curve 2: Des +/+; and curve 4: Des −/−). (C) The muscular endurance was analyzed by measuring the time that animals could hold onto a 32-g bar, either with all four limbs (4L) or with the two forelimbs (2L). Results are expressed in s. (D) Motor coordination: performances were measured either by measuring the time that mice need to cross a rod or by putting the mice on a rotating apparatus. Capacity of Des −/− mice are considerably modified. (E) CMAP measured in gastrocnemius and plantaris muscles from 5-mo-old mice. Results are expressed in mV. (F) Nerve conduction rate measured in gastrocnemius and plantaris muscles from 5-mo-old mice. The DL is given in ms. Data are the means ± standard errors computed from each set of experiments.

Mentions: The first analysis measured the maximum force that could be developed by the Des −/−, Des +/−, and Des +/+ mice (Fig. 9 A). The animals were allowed to catch a bar with either all four limbs or with the two forelimbs. The mice were then pulled out by the tail until they released the bar. The maximum force was significantly reduced by a factor of two in the homozygous Des −/− mice, compared to the wild-type mice (14 mN ± 1 compared to 24 mN ± 1.5 for four limbs, and 4.2 mN ± 0.7 compared to 10). The Fisher test gave a value of P < 0.01 for the four-limb experiment and P < 0.05 for the two-limb experiment. There was no significant difference for the maximum force generated between the heterozygous Des +/− mice and the wild-type mice.


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)

Analyses of muscular performances on control animal  Des +/+ (white), heterozygous Des +/− (hatched) and homozygous Des −/− (black). (A) The maximum force developed by the  mice was measured by pulling the mouse backwards by the tail  until the bar was released. Animals were allowed to hold the bar  linked to a dynamometer either with all four limbs or with the  two forelimbs. Results are expressed in mN. (B) The maximum  force developed by isolated muscle was measured on soleus from  2- (curve 1: Des +/+; curve 3: Des−/−) and 5-mo-old mice  (curve 2: Des +/+; and curve 4: Des −/−). (C) The muscular endurance was analyzed by measuring the time that animals could  hold onto a 32-g bar, either with all four limbs (4L) or with the  two forelimbs (2L). Results are expressed in s. (D) Motor coordination: performances were measured either by measuring the  time that mice need to cross a rod or by putting the mice on a rotating apparatus. Capacity of Des −/− mice are considerably  modified. (E) CMAP measured in gastrocnemius and plantaris  muscles from 5-mo-old mice. Results are expressed in mV. (F)  Nerve conduction rate measured in gastrocnemius and plantaris  muscles from 5-mo-old mice. The DL is given in ms. Data are the  means ± standard errors computed from each set of experiments.
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Related In: Results  -  Collection

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Figure 9: Analyses of muscular performances on control animal Des +/+ (white), heterozygous Des +/− (hatched) and homozygous Des −/− (black). (A) The maximum force developed by the mice was measured by pulling the mouse backwards by the tail until the bar was released. Animals were allowed to hold the bar linked to a dynamometer either with all four limbs or with the two forelimbs. Results are expressed in mN. (B) The maximum force developed by isolated muscle was measured on soleus from 2- (curve 1: Des +/+; curve 3: Des−/−) and 5-mo-old mice (curve 2: Des +/+; and curve 4: Des −/−). (C) The muscular endurance was analyzed by measuring the time that animals could hold onto a 32-g bar, either with all four limbs (4L) or with the two forelimbs (2L). Results are expressed in s. (D) Motor coordination: performances were measured either by measuring the time that mice need to cross a rod or by putting the mice on a rotating apparatus. Capacity of Des −/− mice are considerably modified. (E) CMAP measured in gastrocnemius and plantaris muscles from 5-mo-old mice. Results are expressed in mV. (F) Nerve conduction rate measured in gastrocnemius and plantaris muscles from 5-mo-old mice. The DL is given in ms. Data are the means ± standard errors computed from each set of experiments.
Mentions: The first analysis measured the maximum force that could be developed by the Des −/−, Des +/−, and Des +/+ mice (Fig. 9 A). The animals were allowed to catch a bar with either all four limbs or with the two forelimbs. The mice were then pulled out by the tail until they released the bar. The maximum force was significantly reduced by a factor of two in the homozygous Des −/− mice, compared to the wild-type mice (14 mN ± 1 compared to 24 mN ± 1.5 for four limbs, and 4.2 mN ± 0.7 compared to 10). The Fisher test gave a value of P < 0.01 for the four-limb experiment and P < 0.05 for the two-limb experiment. There was no significant difference for the maximum force generated between the heterozygous Des +/− mice and the wild-type mice.

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