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12 April 2019 Chimeric Mice with Deletion of Cfl2 that Encodes Muscle-Type Cofilin (MCF or Cofilin-2) Results in Defects of Striated Muscles, Both Skeletal and Cardiac Muscles
Kurato Mohri, Fumie Suzuki-Toyota, Takashi Obinata, Naruki Sato
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Abstract

Cofilin, a member of the ADF/cofilin family, is an actin-binding protein which is widely distributed among eukaryotic organisms and involved in actin filament dynamics in a variety of cell types. In mammalian striated muscles, muscle-type cofilin (MCF or cofilin-2) is predominantly expressed. Previous investigations have shown that MCF plays an essential role in the regulation of assembly of contractile apparatus in skeletal muscle, but its role in cardiac muscle has remained unclear. In the present study, in order to further clarify the role of MCF in organization of myofibrillar structure in vivo, we generated chimeric mice with a combination of MCF-deficient cells that were generated by Cfl2-knockout (Cfl2-/-) and wild type cells containing MCF, and examined the effect of MCF deficiency on striated muscles, especially on the fine structures of contractile apparatus in cardiac muscle. We found that mice chimeric for MCF deficient cells exhibited structural defects in their skeletal muscles as previously reported. Histological analysis showed that MCF deficiency leads to degradation of myofibers and promotion of muscle regeneration. Electron microscopic observation of cardiac muscle of the chimeric mice showed coexistence of the cells with normal sarcomeres and those with disorganized myofibrils in a chimeric pattern. In these cofilin-deficient cells, myofilaments were scattered in the cytoplasm and myofibrillar structures were severely disrupted. These results provide strong evidence for that MCF plays a critical role in the formation and the maintenance of myofibril structure not only in skeletal muscle but also in cardiac muscle.

© 2019 Zoological Society of Japan
Kurato Mohri, Fumie Suzuki-Toyota, Takashi Obinata, and Naruki Sato "Chimeric Mice with Deletion of Cfl2 that Encodes Muscle-Type Cofilin (MCF or Cofilin-2) Results in Defects of Striated Muscles, Both Skeletal and Cardiac Muscles," Zoological Science 36(2), 112-119, (12 April 2019). https://doi.org/10.2108/zs180151
Received: 20 September 2018; Accepted: 23 November 2018; Published: 12 April 2019
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KEYWORDS
cardiac muscle
Cfl2
chimeric mice
cofilin
cofilin-2
myofibril assembly
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