scholarly journals Increased Expression of Wild-Type or a Centronuclear Myopathy Mutant of Dynamin 2 in Skeletal Muscle of Adult Mice Leads to Structural Defects and Muscle Weakness

2011 ◽  
Vol 178 (5) ◽  
pp. 2224-2235 ◽  
Author(s):  
Belinda S. Cowling ◽  
Anne Toussaint ◽  
Leonela Amoasii ◽  
Pascale Koebel ◽  
Arnaud Ferry ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Weakness ◽  
Structural Defects ◽  
Centronuclear Myopathy ◽  
Wild Type ◽  
Adult Mice ◽  
Dynamin 2

scholarly journals Nuclear defects in skeletal muscle from a Dynamin 2-linked centronuclear myopathy mouse model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anaïs Fongy ◽  
Sestina Falcone ◽  
Jeanne Lainé ◽  
Bernard Prudhon ◽  
Aurea Martins-Bach ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mouse Model ◽  
Centronuclear Myopathy ◽  
Dynamin 2

scholarly journals Progressive Structural Defects in Canine Centronuclear Myopathy Indicate a Role for HACD1 in Maintaining Skeletal Muscle Membrane Systems

2017 ◽  
Vol 187 (2) ◽  
pp. 441-456 ◽  
Author(s):  
Gemma L. Walmsley ◽  
Stéphane Blot ◽  
Kerrie Venner ◽  
Caroline Sewry ◽  
Jocelyn Laporte ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Structural Defects ◽  
Muscle Membrane ◽  
Centronuclear Myopathy ◽  
Membrane Systems

A novel mutation in the DNM2 gene impairs dynamin 2 localization in skeletal muscle of a patient with late onset centronuclear myopathy

2013 ◽  
Vol 23 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Biruta Kierdaszuk ◽  
Mariusz Berdynski ◽  
Justyna Karolczak ◽  
Maria Jolanta Redowicz ◽  
Cezary Zekanowski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Late Onset ◽  
Novel Mutation ◽  
Centronuclear Myopathy ◽  
Dynamin 2

scholarly journals Overexpression of NF90-NF45 Represses Myogenic MicroRNA Biogenesis, Resulting in Development of Skeletal Muscle Atrophy and Centronuclear Muscle Fibers

2015 ◽  
Vol 35 (13) ◽  
pp. 2295-2308 ◽  
Author(s):  
Hiroshi Todaka ◽  
Takuma Higuchi ◽  
Ken-ichi Yagyu ◽  
Yasunori Sugiyama ◽  
Fumika Yamaguchi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Muscle Fibers ◽  
Negative Regulator ◽  
Skeletal Muscle Atrophy ◽  
Mirna Biogenesis ◽  
Centronuclear Myopathy ◽  
Causative Gene ◽  
Dynamin 2

MicroRNAs (miRNAs) are involved in the progression and suppression of various diseases through translational inhibition of target mRNAs. Therefore, the alteration of miRNA biogenesis induces several diseases. The nuclear factor 90 (NF90)-NF45 complex is known as a negative regulator in miRNA biogenesis. Here, we showed that NF90-NF45 double-transgenic (dbTg) mice develop skeletal muscle atrophy and centronuclear muscle fibers in adulthood. Subsequently, we found that the levels of myogenic miRNAs, including miRNA 133a (miR-133a), which promote muscle maturation, were significantly decreased in the skeletal muscle of NF90-NF45 dbTg mice compared with those in wild-type mice. However, levels of primary transcripts of the miRNAs (pri-miRNAs) were clearly elevated in NF90-NF45 dbTg mice. This result indicated that the NF90-NF45 complex suppressed miRNA production through inhibition of pri-miRNA processing. This finding was supported by the fact that processing of pri-miRNA 133a-1 (pri-miR-133a-1) was inhibited via binding of NF90-NF45 to the pri-miRNA. Finally, the level of dynamin 2, a causative gene of centronuclear myopathy and concomitantly a target of miR-133a, was elevated in the skeletal muscle of NF90-NF45 dbTg mice. Taken together, we conclude that the NF90-NF45 complex induces centronuclear myopathy through increased dynamin 2 expression by an NF90-NF45-induced reduction of miR-133a expressionin vivo.

scholarly journals Imaging-based evaluation of pathogenicity by novel DNM2 variants associated with centronuclear myopathy

2021 ◽  
Author(s):  
Kenshiro Fujise ◽  
Mariko Okubo ◽  
Tadashi Abe ◽  
Hiroshi Yamada ◽  
Kohji Takei ◽  
...  
Keyword(s):  
Disease Progression ◽  
Muscle Weakness ◽  
Quantitative Data ◽  
Clinical Information ◽  
Definitive Diagnosis ◽  
Centronuclear Myopathy ◽  
Membrane Remodeling ◽  
Causative Gene ◽  
T Tubules ◽  
Dynamin 2

ABSTRACTCentronuclear myopathy (CNM) is characterized clinically by muscle weakness and pathologically by the presence of centralized nuclei and disarrangement of T-tubules in muscle fibers. DNM2 which encodes a large GTPase dynamin 2 have been identified as a causative gene for CNM. Nevertheless, the identification of DNM2 variants may not always lead to the definitive diagnosis as their pathogenicity is often unknown.In this study, by imaging T-tubule-like structures reconstituted in cellulo, we demonstrated that aberrant membrane remodeling by mutant dynamin 2 is tightly associated with gain-of-function features of DNM2 variants. This simple in cellulo assay provided quantitative data required for accurately evaluating pathogenicity of reported and novel DNM2 variants identified from CNM patients in our cohort. Our approaches combining the in cellulo assay with clinical information of the patients enabled to explain the course of a disease progression by pathogenesis of each variant in DNM2-associated CNM.

scholarly journals β-Actin shows limited mobility and is required only for supraphysiological insulin-stimulated glucose transport in young adult soleus muscle

2018 ◽  
Vol 315 (1) ◽  
pp. E110-E125 ◽  
Author(s):  
Agnete B. Madsen ◽  
Jonas R. Knudsen ◽  
Carlos Henriquez-Olguin ◽  
Yeliz Angin ◽  
Kristien J. Zaal ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Young Adult ◽  
Actin Cytoskeleton ◽  
Glucose Transport ◽  
Wild Type ◽  
Mouse Muscle ◽  
Mature Adult ◽  
Adult Mice ◽  
Actin Isoform

Studies in skeletal muscle cell cultures suggest that the cortical actin cytoskeleton is a major requirement for insulin-stimulated glucose transport, implicating the β-actin isoform, which in many cell types is the main actin isoform. However, it is not clear that β-actin plays such a role in mature skeletal muscle. Neither dependency of glucose transport on β-actin nor actin reorganization upon glucose transport have been tested in mature muscle. To investigate the role of β-actin in fully differentiated muscle, we performed a detailed characterization of wild type and muscle-specific β-actin knockout (KO) mice. The effects of the β-actin KO were subtle; however, we confirmed the previously reported decline in running performance of β-actin KO mice compared with wild type during repeated maximal running tests. We also found insulin-stimulated glucose transport into incubated muscles reduced in soleus but not in extensor digitorum longus muscle of young adult mice. Contraction-stimulated glucose transport trended toward the same pattern, but the glucose transport phenotype disappeared in soleus muscles from mature adult mice. No genotype-related differences were found in body composition or glucose tolerance or by indirect calorimetry measurements. To evaluate β-actin mobility in mature muscle, we electroporated green fluorescent protein (GFP)-β-actin into flexor digitorum brevis muscle fibers and measured fluorescence recovery after photobleaching. GFP-β-actin showed limited unstimulated mobility and no changes after insulin stimulation. In conclusion, β-actin is not required for glucose transport regulation in mature mouse muscle under the majority of the tested conditions. Thus, our work reveals fundamental differences in the role of the cortical β-actin cytoskeleton in mature muscle compared with cell culture.

scholarly journals Type II iodothyronine deiodinase provides intracellular 3,5,3′-triiodothyronine to normal and regenerating mouse skeletal muscle

2011 ◽  
Vol 301 (5) ◽  
pp. E818-E824 ◽  
Author(s):  
Alessandro Marsili ◽  
Dan Tang ◽  
John W. Harney ◽  
Prabhat Singh ◽  
Ann Marie Zavacki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Normal Mouse ◽  
Primary Cultures ◽  
Type Ii ◽  
Wild Type ◽  
Iodothyronine Deiodinase ◽  
Mouse Skeletal Muscle ◽  
Adult Mice ◽  
Liver And Kidney ◽  
The Difference

The FoxO3-dependent increase in type II deiodinase (D2), which converts the prohormone thyroxine (T4) to 3,5,3′-triiodothyronine (T3), is required for normal mouse skeletal muscle differentiation and regeneration. This implies a requirement for an increase in D2-generated intracellular T3 under these conditions, which has not been directly demonstrated despite the presence of D2 activity in skeletal muscle. We directly show that D2-mediated T4-to-T3 conversion increases during differentiation in C2C12 myoblast and primary cultures of mouse neonatal skeletal muscle precursor cells, and that blockade of D2 eliminates this. In adult mice given 125I-T4 and 131I-T3, the intracellular 125I-T3/131I-T3 ratio is significantly higher than in serum in both the D2-expressing cerebral cortex and the skeletal muscle of wild-type, but not D2KO, mice. In D1-expressing liver and kidney, the 125I-T3/131I-T3 ratio does not differ from that in serum. Hypothyroidism increases D2 activity, and in agreement with this, the difference in 125I-T3/131I-T3 ratio is increased further in hypothyroid wild-type mice but not altered in the D2KO. Notably, in wild-type but not in D2KO mice, the muscle production of 125I-T3 is doubled after skeletal muscle injury. Thus, D2-mediated T4-to-T3 conversion generates significant intracellular T3 in normal mouse skeletal muscle, with the increased T3 required for muscle regeneration being provided by increased D2 synthesis, not by T3 from the circulation.

scholarly journals A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice

2010 ◽  
Vol 19 (24) ◽  
pp. 4820-4836 ◽  
Author(s):  
Anne-Cécile Durieux ◽  
Alban Vignaud ◽  
Bernard Prudhon ◽  
Mai Thao Viou ◽  
Maud Beuvin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Structure And Function ◽  
Centronuclear Myopathy ◽  
Muscle Structure ◽  
And Function ◽  
Dynamin 2

Phenotype characterization in patients with dynamin 2 related centronuclear myopathy

2010 ◽  
Vol 41 (01) ◽  
Author(s):  
F Hanisch ◽  
A Dietz ◽  
T Grimm ◽  
M Bitoun ◽  
S Zierz
Keyword(s):  
Centronuclear Myopathy ◽  
Phenotype Characterization ◽  
Dynamin 2

Tropomyosin mutations responsible for muscle weakness in inherited skeletal muscle diseases

2008 ◽  
pp. 20-21
Author(s):  
Julien Ochala ◽  
Anders Oldfors ◽  
Lars Larsson
Keyword(s):  
Skeletal Muscle ◽  
Muscle Weakness ◽  
Muscle Diseases
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