Alterations in contractile properties and expression of myofibrillar proteins in wobbler mouse muscles.

The purpose of this study was to characterize the alterations in muscle contractile (tension-pCa relationship) and biochemical (myosin heavy and light chains, troponin C content) properties in a hereditary motoneuron disease. The study was performed on wobbler mouse mutants which presented a neuronal degeneration. The time course of the disease was followed at 5 and 7 weeks in sternocleidomastoid (SCM) and soleus muscles. The wobbler disease was found to induce a shift from fast to slow myosin heavy-chain isoform expression in SCM and soleus muscles. The analysis of the myosin light-chain (MLC) composition revealed, for the SCM muscles, the appearance of the slow isoforms at 5 weeks and an increase in the regulatory MLC2 content at 7 weeks. A significant increase in the slow troponin C isoform content was found in both types of wobbler muscles at 7 weeks. The wobbler soleus and SCM muscles presented an age- and fiber-type-related atrophy, characterized by a decline in absolute maximal tension and fiber diameter. A decrease in calcium sensitivity was observed at 7 weeks for the soleus fibers and at both 5 and 7 weeks for the SCM. The results indicated fast-to-slow changes in contractile and biochemical properties of the wobbler soleus and SCM muscles, which occurred during the motoneuron degeneration process previously described in the wobbler pathology.

Toursel T ，Bastide B ，Stevens L ，Rieger F ，Mounier Y ... -  《EXPERIMENTAL NEUROLOGY》

Coordinate changes of myosin light and heavy chain isoforms during forced fiber type transitions in rabbit muscle.

Leeuw T ，Pette D 《developmental genetics》

Nerve influence on myosin light chain phosphorylation in slow and fast skeletal muscles.

Bozzo C ，Spolaore B ，Toniolo L ，Stevens L ，Bastide B ，Cieniewski-Bernard C ，Fontana A ，Mounier Y ，Reggiani C ... -  《FEBS Journal》

Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age.

Gannon J ，Doran P ，Kirwan A ，Ohlendieck K ... -  《-》

Neuro-muscular function in the wobbler murine model of primary motor neuronopathy.

The wobbler mouse represents a model for neurodegenerative disease affecting motor neurons. This study explored the importance of fiber type specific changes for the contractile dysfunction of soleus and extensor digitorum longus (EDL) muscles from wobbler mice using a specific inhibitor of force generation by the type II myosin protein. Generally, wobbler condition was associated with ~50% reductions in muscle mass and contractile capacity in both muscles. In soleus, an increase in the relative abundance of type I myosin protein was observed. Since, however, only ~40% of the fibers containing type I myosin had functional innervation whereas almost all fibers containing type II myosin were innervated, the shift toward type I myosin was without significance for the in vivo contractile phenotype. Soleus muscles from wobbler mice were further characterized by a 2-fold increase in the width of the twitches, which was associated with a reduction in the excitation frequency necessary to elicit tetanic contractions. Since the SR Ca(2+) ATPase in wobbler soleus was reduced from 22 ± 5 to 10 ± 2 nmol/g muscle tissue (P=0.0006), the increase in twitch width was most likely caused by delayed recovery of cytosolic Ca(2+). Such changes were not observed in EDL. It is concluded that the shift in myosin protein from type II to type I previously reported in both innervated and denervated wobbler muscles primarily takes place in the population of denervated muscle fibers. Since these muscles do not contribute to force generation, the transition is, therefore, of limited relevance for the contractile phenotype of the muscles. Instead, the slow contractile phenotype of wobbler soleus muscles seemed to be a consequence of reduced SR content of Ca(2+) ATPase.

Broch-Lips M ，Pedersen TH ，Riisager A ，Schmitt-John T ，Nielsen OB ... -  《-》