Desmin Is Essential for the Tensile Strength and Integrity of Myofibrils but Not for Myogenic Commitment, Differentiation, and Fusion of Skeletal Muscle

Abstract

A null 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.

Contractile function, sarcolemma integrity, and the loss of dystrophin after skeletal muscle eccentric contraction-induced injury

“…In that study, the extensor digitorum longus (EDL) had an immediate loss of desmin, and it was only after 15 min of repeated contractions that the TA showed a significant loss in desmin, indicating that anatomical and biomechanical variables are likely important. Like muscles in dystrophin-knockout mice, muscles in desmin-knockout mice are reported to be more vulnerable to eccentric injury (29), although a different study indicates that muscles in desmin-knockout mice are much less vulnerable to injury than controls (44). Such disparate findings illustrate the present lack of full understanding we have for these various cytoskeletal proteins.…”

Characterization of proliferating human skeletal muscle‐derived cells in vitro: Differential modulation of myoblast markers by TGF‐β2

“…Desmin and creatine kinase have been attributed functional roles in mature myocytes and are highly expressed in muscle (Shainberg et al, 1971;Li et al, 1997). Desmin expression in proliferating myoblasts is governed by a 5 0 proximal promoter region (myoblastspecific region), and its elevated expression during differentiation is governed by a 5 0 distal enhancer (myotube-specific region) that contains an E-box commonly found in muscle-specific genes (Wentworth et al, 1991;Li and Paulin, 1993).…”

Amino‐terminally truncated desmin rescues fusion of des−/− myoblasts but negatively affects cardiomyogenesis and smooth muscle development

“…Knock-out of the desmin gene demonstrated its signi¢cant roles in cardiac, skeletal and smooth muscle function [5,17,18]. Here we reported that desmin v1À48 lacking 48 amino acids of the amino-terminal head domain a¡ects cardiac, skeletal and smooth muscle to di¡erent degrees in EBs thus demonstrating that desmin exerts di¡erent roles via its head domain during muscle development.…”