Filamin C accumulation is a strong but nonspecific immunohistochemical marker of core formation in muscle

Bönnemann, Carsten G.; Thompson, Terri G.; Ven, Peter F.M. van der; Goebel, Hans H.; Warlo, Irene; Vollmers, B; Reimann, Jens; Herms, Jochen; Gautel, Mathias; Takada, Fumio; Beggs, Alan H.; Fürst, Dieter O.; Kunkel, Louis M.; Hanefeld, F.; Schröder, Rolf

doi:10.1016/s0022-510x(02)00341-6

Cited by 56 publications

(35 citation statements)

References 42 publications

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“…Several studies have reported an abnormal localization of filamin C in a number of muscle diseases (17,76), and its mutation has been associated with a novel form of myofibrillar myopathy (26). Despite its reported role in muscle differentiation and maintenance of elongated muscle fiber structure (26), the precise function of filamin C in skeletal muscle plasticity remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures

Chopard

LeCunff

Danger

et al. 2009

Physiological Genomics

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Chopard A, Lecunff M, Danger R, Lamirault G, Bihouee A, Teusan R, Jasmin BJ, Marini JF, Leger JJ. Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures. Physiol Genomics 38: 291-302, 2009. First published May 26, 2009 doi:10.1152/physiolgenomics.00036.2009.-Microgravity has a dramatic impact on human physiology, illustrated in particular, with skeletal muscle impairment. A thorough understanding of the mechanisms leading to loss of muscle mass and structural disorders is necessary for defining efficient clinical and spaceflight countermeasures. We investigated the effects of long-term bed rest on the transcriptome of soleus (SOL) and vastus lateralis (VL) muscles in healthy women (BRC group, n ϭ 8), and the potential beneficial impact of protein supplementation (BRN group, n ϭ 8) and of a combined resistance and aerobic training (BRE group, n ϭ 8). Gene expression profiles were obtained using a customized microarray containing 6,681 muscles-relevant genes. A two-class statistical analysis was applied on 2,103 genes with consolidated expression in BRC, BRN, and BRE groups. We identified 472 and 207 mRNAs whose expression was modified in SOL and VL from BRC group, respectively. Further clustering analysis, identifying relevant biological mechanisms and pathways, reported five main subclusters. Three are composed of upregulated mRNAs involved mainly in nucleic acid and protein metabolism, and two made up of downregulated transcripts encoding components involved in energy metabolism. Exercise countermeasure demonstrated drastic compensatory effects, decreasing the number of differentially expressed mRNAs by 89 and 96% in SOL and VL, respectively. In contrast, nutrition countermeasure had moderate effects and decreased the number of differentially-expressed transcripts by 40 and 25% in SOL and VL. Together, these data present a systematic, global and comprehensive view of the adaptive response of female muscle to long-term atrophy.skeletal muscle fiber; atrophy; microgravity; microarray; leucine SKELETAL MUSCLE IS ONE OF the most affected tissues in disuse situations since it can exhibit large structural and functional adaptations, depending on changes in the levels of imposed mechanical constraints (1). Neuromuscular activity is decreased by hypokinesia and hypodynamia, as well by microgravity environment resulting in skeletal muscle atrophy (35). Space exploration and interplanetary travel requires that humans be confronted with extended durations of space environment and weightlessness. From a few days in space (with the Mercury, Gemini, and Apollo-Soyouz programs), to several months in a space station (with Skylab, MIR, and the actual ISS), disuse-induced muscle atrophy and impairment is a biomedical challenge and a focus point of space sciences in studying the deleterious effects of microgravity (1,27,35).Human bed rest (BR), a ground-based model, provides an opportunity to understand the components of musc...

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Section: Discussionmentioning

confidence: 99%

Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures

Chopard

LeCunff

Danger

et al. 2009

Physiological Genomics

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“…FLNc localization is abnormal in a number of muscle diseases (3,19,24), and a mutation in FLNc has recently been associated with a novel form of myofibrillar myopathy (28).…”

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Loss of FilaminC (FLNc) Results in Severe Defects in Myogenesis and Myotube Structure

Dalkilic

Schienda

Thompson

et al. 2006

Molecular and Cellular Biology

151

130

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FilaminC (FLNc) is the muscle-specific member of a family of actin binding proteins. Although it interacts with many proteins involved in muscular dystrophies, its unique role in muscle is poorly understood. To address this, two models were developed. First, FLNc expression was stably reduced in C2C12 myoblasts by RNA interference. While these cells start differentiation normally, they display defects in differentiation and fusion ability and ultimately form multinucleated "myoballs" rather than maintain elongated morphology. Second, a mouse model carrying a deletion of last 8 exons of Flnc was developed. FLNc-deficient mice die shortly after birth, due to respiratory failure, and have severely reduced birth weights, with fewer muscle fibers and primary myotubes, indicating defects in primary myogenesis. They exhibit variation in fiber size, fibers with centrally located nuclei, and some rounded fibers resembling the in vitro phenotype. The similarity of the phenotype of FLNc-deficient mice to the filamin-interacting TRIO null mice was further confirmed by comparing FLNc-deficient C2C12 cells to TRIO-deficient cells. These data provide the first evidence that FLNc has a crucial role in muscle development and maintenance of muscle structural integrity and suggest the presence of a TRIO-FLNcdependent pathway in maintaining proper myotube structure.

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“…We are thus in accordance with the guidelines of MmD consortium 1 that recommended electron microscopy as one of the criteria for diagnosis. Immunohistochemistry may help by demonstrating filamin C and alpha-B-crystallin within the minicores, where they react stronger than desmin 26 .…”

Section: Discussionmentioning

confidence: 99%

Multi-minicore disease revisited

Nucci

Queiroz

Zambelli

et al. 2004

Arq. Neuro-Psiquiatr.

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-Multi-minicore disease (MmD) is an infrequent congenital myopathy, defined by structural changes in optic and electron microscopy, namely, multiple small areas lacking oxidative enzyme activity and focal disorganization of contractile proteins involving at most a few sarcomeres. The classical form of the disease manifests as more or less severe hypotonia and generalized weakness with predominance in axial and proximal limb muscles. Clinical variants also exist. Usually MmD is inherited as an autosomal recessive trait. Genetic heterogeneity is recognized and up to now mutations in the genes of RYR1 and SEPN1 have been detected. We record three unrelated cases of MmD. Case 1, with the classical benign form, was followedup for 15 years. Case 2, presenting pharyngolaryngeal involvement and severe delay of head control, improved gradually, until independent gait was acquired at age of six years. A moderate restriction of daily life activities remains. Case 3, of antenatal-onset, was expressed by arthrogryposis of hands, predominance of scapular girdle deficit and a stable course after ten years on physiotherapy. All cases were selected by the characteristic morphological abnormalities in biceps brachii samples, including electron microscopy. Emphasis is given to case 2 due to type 1 fiber uniformity and mild endomysial fibrosis, posing a difficult differential diagnosis with congenital muscular dystrophy were it not for the significant number of multi-minicores.KEY WORDS: congenital myopathy, multi-minicore disease, phenotype, histochemistry, electron microscopy. Miopatia dos multi-minifocos revisitadaRESUMO -A miopatia dos múltiplos minifocos (MM) é doença congênita rara, definida por alterações estruturais observadas ao microscópio óptico e eletrônico: múltiplas e pequenas áreas sem atividade enzimática oxidativa e desorganização focal das proteínas contráteis envolvendo poucos sarcômeros. A forma clássi-ca da doença se manifesta com hipotonia mais ou menos grave e fraqueza generalizada, predominante em músculos axiais e proximais em membros. Entretanto, variantes clínicas existem. A MM é usualmente herdada como traço autossômico recessivo. Heterogeneidade genética tem sido reconhecida e até o momento mutações nos genes RYR1 e SEPN1 foram detectadas. Relatamos três casos de MM. Caso 1, que tem a forma clássica e benigna da doença, assim permaneceu ao longo de 15 anos. Caso 2 apresentou envolvimento faringo-laríngeo e grave atraso no controle cefálico que melhorou gradualmente, até que a deambulação plena foi adquirida aos seis anos; permanece com moderada limitação das atividades da vida diária. Caso 3 teve início pré-natal, expresso através de artrogripose das mãos. Havia predominância de déficit em cintura escapular e o curso tem sido estável, com fisioterapia, por 10 anos. Os casos foram selecionados pelas características morfológicas na biópsia do biceps braquial que incluiu microscopia eletrônica. Enfatizamos, no caso 2, a uniformidade das fibras do tipo 1 e a leve fibrose do endomísio, tendo sido ne...

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Filamin C accumulation is a strong but nonspecific immunohistochemical marker of core formation in muscle

Cited by 56 publications

References 42 publications

Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures

Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures

Loss of FilaminC (FLNc) Results in Severe Defects in Myogenesis and Myotube Structure

Multi-minicore disease revisited

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