Knockout of zebrafish desmin genes does not cause skeletal muscle degeneration but alters calcium flux

Kürekçi, Gülsüm Kayman; Mangit, Ecem Kural; Koyunlar, Cansu; Unsal, Seyda; Saglam, Berk; Ergin, Bora; Gizer, Merve; Uyanik, Ismail; Düz, Niloufar Boustanabadimaralan; Korkusuz, Petek; Talim, Beril; Puralı, Nuhan; Hughes, Simon M.; Dinçer, Pervin

doi:10.1038/s41598-021-86974-w

Cited by 19 publications

(19 citation statements)

References 38 publications

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“…6F, 5 dpf; and Fig. 6G, 7 dpf), we observed two DES bands (an upper band ~55 kDa and a lower band ~50 kDa), consistent with a previous report in adult zebrafish muscle (Kayman Kürekçi et al, 2021). In the mutants, we detected significant DES upregulation in both 5 dpf speg-DKO zebrafish (2-2.5 fold, Fig.…”

Section: Speg Deficiency Disrupts Ecc and Impairs Zebrafish Swimming Performancesupporting

confidence: 91%

“…3-5), 2) mtm1-KO at 7 dpf (Sabha et al, 2016), and 3) DNM2-S619L-eGFP transgenics at 3 dpf (Zhao et al, 2019). To examine DES localization, we stained isolated myofibres with a DES antibody that picks up both Desmin-a and Desmin-b in zebrafish (Kayman Kürekçi et al, 2021). In myofibres from WT zebrafish, DES forms transverse striations marking the sarcomeric Z-disks, and is also localized around the nucleus and below the sarcolemma (Fig.…”

Section: Speg Deficiency Disrupts Ecc and Impairs Zebrafish Swimming Performancementioning

confidence: 99%

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A novel zebrafish model of SPEG-related centronuclear myopathy (CNM): characterization and comparison with other CNM model zebrafish

Espinosa

Geissah

Groom

et al. 2021

Preprint

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Centronuclear myopathy (CNM) is a congenital neuromuscular disorder caused by pathogenic variation in genes associated with membrane trafficking and excitation-contraction coupling (ECC). Bi-allelic autosomal recessive mutations in striated muscle enriched protein kinase (SPEG) account for a subset of CNM patients. Previous research has been limited by the perinatal lethality of Speg knockout mice. Thus, the precise biological role of SPEG in skeletal muscle remains unknown. To address this issue, we generated zebrafish spega, spegb, and spega/spegb (speg-DKO) mutant lines. We demonstrate that speg-DKO zebrafish faithfully recapitulate multiple phenotypes associated with human CNM, including disruption of the ECC protein machinery, dysregulation of calcium homeostasis during ECC, and impairment of muscle performance. Taking advantage of the availability of zebrafish models of multiple CNM genetic subtypes, we compared novel and known disease markers in speg-DKO with mtm1-KO and DNM2-S619L transgenic zebrafish. We observed desmin (DES) accumulation common to all CNM subtypes, and Dnm2 upregulation in muscle of both speg-DKO and mtm1-KO zebrafish. In all, we establish a new model of SPEG-related CNM, and identify abnormalities in this model suitable for defining disease pathomechanisms and evaluating potential therapies.

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Section: Speg Deficiency Disrupts Ecc and Impairs Zebrafish Swimming Performancesupporting

confidence: 91%

Section: Speg Deficiency Disrupts Ecc and Impairs Zebrafish Swimming Performancementioning

confidence: 99%

A novel zebrafish model of SPEG-related centronuclear myopathy (CNM): characterization and comparison with other CNM model zebrafish

Espinosa

Geissah

Groom

et al. 2021

Preprint

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show abstract

“…More recently, a zebrafish knockout model has been created using CRISPR: fish are also viable but with a subtle phenotype of calcium sensitivity. 41 These results contrast the previous results obtained with zebrafish morpholino-based desmin knockdown 88 or with knockins, 89 which showed a highly damaged phenotype. Some of the alterations could be attributed to the morpholinos because they are known to disturb development.…”

Section: Functionscontrasting

confidence: 76%

What does desmin do: A bibliometric assessment of the functions of the muscle intermediate filament

Gomes

Seixas

Azevedo

et al. 2022

Exp Biol Med (Maywood)

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Intermediate filaments were first described in muscle in 1968, and desmin was biochemically identified about 10 years afterwards. Its importance grew after the identification of desminopathies and desmin mutations that cause mostly cardiopathies. Since its characterization until recently, different functions have been attributed to desmin. Here, we use bibliometric tools to evaluate the articles published about desmin and to assess its several putative functions. We identified the most productive authors and the relationships between research groups. We studied the more frequent words among 9734 articles (September 2021) containing “desmin” on the title and abstract, to identify the major research focus. We generated an interactive spreadsheet with the 934 papers that contain “desmin” only on the title that can be used to search and quantify terms in the abstract. We further selected the articles that contained the terms “function” or “role” from the spreadsheet, which we then classified according to type of function, organelle, or tissue involved. Based on the bibliographic analysis, we assess comparatively the putative functions, and we propose an alternative explanation for the desmin function.

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“…We thus compared Desmin expression in a series of CNM zebrafish models at stages at which muscle phenotypes are fully penetrant: (1) speg -DKO at 5-7 dpf ( Figs 3 – 5 ), (2) mtm1 -KO at 7 dpf ( Sabha et al, 2016 ) and (3) DNM2 -S619L-eGFP transgenics at 3 dpf ( Zhao et al, 2019 ). To examine Desmin localization, we stained isolated myofibers with an anti-Desmin antibody that picks up both Desmin-a and Desmin-b in zebrafish ( Kayman Kürekçi et al, 2021 ). In myofibers from WT zebrafish, Desmin formed transverse striations marking the sarcomeric Z-disks, and was also localized around the nucleus and below the sarcolemma ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Characterization of a novel zebrafish model of SPEG-related centronuclear myopathy

Espinosa

Geissah

Groom

et al. 2022

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Centronuclear myopathy (CNM) is a congenital neuromuscular disorder caused by pathogenic variation in genes associated with membrane trafficking and excitation-contraction coupling (ECC). Bi-allelic autosomal recessive mutations in striated muscle enriched protein kinase (SPEG) account for a subset of CNM patients. Previous research has been limited by the perinatal lethality of constitutive Speg knockout mice. Thus, the precise biological role of SPEG in developing skeletal muscle remains unknown. To address this issue, we generated zebrafish spega, spegb, and spega;spegb (speg-DKO) mutant lines. We demonstrate that speg-DKO zebrafish faithfully recapitulate multiple phenotypes associated with CNM, including disruption of the ECC machinery, dysregulation of calcium homeostasis during ECC, and impairment of muscle performance. Taking advantage of zebrafish models of multiple CNM genetic subtypes, we compared novel and known disease markers in speg-DKO with mtm1-KO and DNM2-S619L transgenic zebrafish. We observed desmin accumulation common to all CNM subtypes, and DNM2 upregulation in muscle of both speg-DKO and mtm1-KO zebrafish. In all, we establish a new model of SPEG-related CNM, and identify abnormalities in this model suitable for defining disease pathomechanisms and evaluating potential therapies.

show abstract

Knockout of zebrafish desmin genes does not cause skeletal muscle degeneration but alters calcium flux

Cited by 19 publications

References 38 publications

A novel zebrafish model of SPEG-related centronuclear myopathy (CNM): characterization and comparison with other CNM model zebrafish

A novel zebrafish model of SPEG-related centronuclear myopathy (CNM): characterization and comparison with other CNM model zebrafish

What does desmin do: A bibliometric assessment of the functions of the muscle intermediate filament

Characterization of a novel zebrafish model of SPEG-related centronuclear myopathy

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