P.9.11 Transgenic zebrafish expressing mutant skeletal muscle actin, acta1a, model human nemaline myopathy

2013 ◽  
Vol 23 (9-10) ◽  
pp. 787 ◽  
Author(s):  
O. Ceyhan ◽  
A.H. Beggs
Keyword(s):  
Skeletal Muscle ◽  
Nemaline Myopathy ◽  
Transgenic Zebrafish ◽  
Muscle Actin

Heterogeneity of nemaline myopathy cases with skeletal muscle ?-actin gene mutations

2004 ◽  
Vol 56 (1) ◽  
pp. 86-96 ◽  
Author(s):  
Pankaj B. Agrawal ◽  
Corinne D. Strickland ◽  
Charles Midgett ◽  
Ana Morales ◽  
Daniel E. Newburger ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Gene Mutations ◽  
Nemaline Myopathy ◽  
Actin Gene ◽  
Muscle Actin ◽  
Muscle Actin Gene

Nemaline myopathy caused by absence of α-skeletal muscle actin

2007 ◽  
Vol 61 (2) ◽  
pp. 175-184 ◽  
Author(s):  
Kristen J. Nowak ◽  
Caroline A. Sewry ◽  
Carmen Navarro ◽  
Waney Squier ◽  
Cristina Reina ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Nemaline Myopathy ◽  
Muscle Actin

scholarly journals Dysregulation of NRAP degradation by KLHL41 contributes to pathophysiology in nemaline myopathy

2019 ◽  
Vol 28 (15) ◽  
pp. 2549-2560 ◽  
Author(s):  
Caroline Jirka ◽  
Jasmine H Pak ◽  
Claire A Grosgogeat ◽  
Michael Mario Marchetii ◽  
Vandana A Gupta
Keyword(s):  
Skeletal Muscle ◽  
Thin Filament ◽  
Muscle Development ◽  
Nemaline Myopathy ◽  
Therapeutic Interventions ◽  
Transgenic Zebrafish ◽  
Anchoring Protein ◽  
And Function

Abstract Nemaline myopathy (NM) is the most common form of congenital myopathy that results in hypotonia and muscle weakness. This disease is clinically and genetically heterogeneous, but three recently discovered genes in NM encode for members of the Kelch family of proteins. Kelch proteins act as substrate-specific adaptors for Cullin 3 (CUL3) E3 ubiquitin ligase to regulate protein turnover through the ubiquitin-proteasome machinery. Defects in thin filament formation and/or stability are key molecular processes that underlie the disease pathology in NM; however, the role of Kelch proteins in these processes in normal and diseases conditions remains elusive. Here, we describe a role of NM causing Kelch protein, KLHL41, in premyofibil-myofibil transition during skeletal muscle development through a regulation of the thin filament chaperone, nebulin-related anchoring protein (NRAP). KLHL41 binds to the thin filament chaperone NRAP and promotes ubiquitination and subsequent degradation of NRAP, a process that is critical for the formation of mature myofibrils. KLHL41 deficiency results in abnormal accumulation of NRAP in muscle cells. NRAP overexpression in transgenic zebrafish resulted in a severe myopathic phenotype and absence of mature myofibrils demonstrating a role in disease pathology. Reducing Nrap levels in KLHL41 deficient zebrafish rescues the structural and function defects associated with disease pathology. We conclude that defects in KLHL41-mediated ubiquitination of sarcomeric proteins contribute to structural and functional deficits in skeletal muscle. These findings further our understanding of how the sarcomere assembly is regulated by disease-causing factors in vivo, which will be imperative for developing mechanism-based specific therapeutic interventions.

scholarly journals α-Skeletal muscle actin nemaline myopathy mutants cause cell death in cultured muscle cells

2009 ◽  
Vol 1793 (7) ◽  
pp. 1259-1271 ◽  
Author(s):  
Drieke Vandamme ◽  
Ellen Lambert ◽  
Davy Waterschoot ◽  
Christian Cognard ◽  
Joël Vandekerckhove ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Muscle Cells ◽  
Nemaline Myopathy ◽  
Muscle Actin

scholarly journals Nemaline Myopathy with Minicores Caused by Mutation of the CFL2 Gene Encoding the Skeletal Muscle Actin–Binding Protein, Cofilin-2

2007 ◽  
Vol 80 (1) ◽  
pp. 162-167 ◽  
Author(s):  
Pankaj B. Agrawal ◽  
Rebecca S. Greenleaf ◽  
Kinga K. Tomczak ◽  
Vilma-Lotta Lehtokari ◽  
Carina Wallgren-Pettersson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Binding Protein ◽  
Nemaline Myopathy ◽  
Actin Binding ◽  
Muscle Actin ◽  
Gene Encoding ◽  
Actin Binding Protein

scholarly journals Dysregulation of NRAP degradation by KLHL41 contributes to pathophysiology in Nemaline Myopathy

2018 ◽  
Author(s):  
Caroline Jirka ◽  
Jasmine H Pak ◽  
Claire A Grosgogeat ◽  
Michael M Marchetti ◽  
Vandana A Gupta
Keyword(s):  
Skeletal Muscle ◽  
Thin Filament ◽  
Muscle Development ◽  
Nemaline Myopathy ◽  
Therapeutic Interventions ◽  
Transgenic Zebrafish ◽  
Sarcomeric Protein ◽  
And Function

Nemaline myopathy (NM) is the most common form of congenital myopathy that results in hypotonia and muscle weakness. This disease is clinically and genetically heterogeneous, but three recently discovered genes in NM encode for members of the Kelch family of proteins. Kelch proteins act as substrate-specific-adapters for CUL3 E3 ubiquitin ligase to regulate protein turn-over through the ubiquitin-proteasome machinery. Defects in thin filament formation and/or stability are key molecular processes that underlie the disease pathology in NM, however, the role of Kelch proteins in these processes in normal and diseases conditions remains elusive in vivo. Here, we describe a role of NM causing Kelch protein, KLHL41, in premyofibil-myofibil transition during skeletal muscle development through a regulation of the thin filament chaperone, NRAP. KLHL41 binds to the thin filament chaperone NRAP and promotes ubiquitination and subsequent degradation of NRAP, a process that is critical for the formation of mature myofibrils. KLHL41 deficiency results in abnormal accumulation of NRAP in muscle cells. NRAP overexpression in transgenic zebrafish resulted in a severe myopathic phenotype and absence of mature myofibrils demonstrating a role in disease pathology. Reducing Nrap levels in KLHL41 deficient zebrafish rescues the structural and function defects associated with disease pathology. We conclude that defects in KLHL41-mediated ubiquitination of sarcomeric protein contribute to structural and functional deficits in skeletal muscle. These findings further our understanding of how the sarcomere assembly is regulated by disease causing factors in vivo, which will be imperative for developing mechanism-based specific therapeutic interventions.

Theoretical studies on capillary microviscometry of skeletal muscle actin

1983 ◽  
Vol 3 (2) ◽  
pp. 195-206
Author(s):  
Mitsuhiko Masuhara ◽  
Hiroyuki Yokoyama ◽  
Noriyuki Tatsumi
Keyword(s):  
Mathematical Model ◽  
Skeletal Muscle ◽  
Large Volume ◽  
Theoretical Studies ◽  
Muscle Actin

For improving Ostwald's viscometry, which is time-consuming and requires a relatively large volume of specimen to determine viscosity, we developed a capillary microviscometric method with an appropriate mathematical model, and have compared this method with Ostwald's method.

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