A zebrafish model to study small-fiber neuropathy reveals a potential role for GDAP1

Eijkenboom, Ivo; Vanoevelen, Jo; Hoeijmakers, Janneke G. J.; Wijnen, Iris; Gerards, Mike; Faber, Catharina G.; Smeets, Hubert J.M.

doi:10.1016/j.mito.2019.01.002

Cited by 14 publications

(9 citation statements)

References 50 publications

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“…Around 25% of gdap1 F0 mutant in-cross offspring exhibited a phenotype resembling the one observed after gdap1 morpholino knock-down described previously [14] (Supplementary Fig. 1), while there was no obvious phenotype in ghitm mutant F1 offspring apparent in the first 5 days of development.…”

Section: Resultssupporting

confidence: 75%

An improved method for precise genome editing in zebrafish using CRISPR-Cas9 technique

et al. 2021

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Current methods of CRISPR-Cas9-mediated site-specific mutagenesis create deletions and small insertions at the target site which are repaired by imprecise non-homologous end-joining. Targeting of the Cas9 nuclease relies on a short guide RNA (gRNA) corresponding to the genome sequence approximately at the intended site of intervention. We here propose an improved version of CRISPR-Cas9 genome editing that relies on two complementary guide RNAs instead of one. Two guide RNAs delimit the intervention site and allow the precise deletion of several nucleotides at the target site. As proof of concept, we generated heterozygous deletion mutants of the kcng4b, gdap1, and ghitm genes in the zebrafish Danio rerio using this method. A further analysis by high-resolution DNA melting demonstrated a high efficiency and a low background of unpredicted mutations. The use of two complementary gRNAs improves CRISPR-Cas9 specificity and allows the creation of predictable and precise mutations in the genome of D. rerio.

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Section: Resultssupporting

confidence: 75%

An improved method for precise genome editing in zebrafish using CRISPR-Cas9 technique

et al. 2021

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“…The alteration of mitochondrial networks in Opa1 morphants has been reported more recently ( 121 ), confirming the main role of OPA1 in mitochondrial morphology.…”

Section: Opa1 Animal Modelssupporting

confidence: 75%

Dominant Optic Atrophy (DOA): Modeling the Kaleidoscopic Roles of OPA1 in Mitochondrial Homeostasis

Dotto

Carelli

2021

Front. Neurol.

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In the year 2000, the discovery of OPA1 mutations as causative for dominant optic atrophy (DOA) was pivotal to rapidly expand the field of mitochondrial dynamics and describe the complex machinery governing this pathway, with a multitude of other genes and encoded proteins involved in neurodegenerative disorders of the optic nerve. OPA1 turned out to be a much more complex protein than initially envisaged, connecting multiple pathways beyond its strict role in mitochondrial fusion, such as sensing of OXPHOS needs and mitochondrial DNA maintenance. As a consequence, an increasing need to investigate OPA1 functions at multiple levels has imposed the development of multiple tools and models that are here reviewed. Translational mitochondrial medicine, with the ultimate objective of translating basic science necessary to understand pathogenic mechanisms into therapeutic strategies, requires disease modeling at multiple levels: from the simplest, like in yeast, to cell models, including the increasing use of reprogrammed stem cells (iPSCs) from patients, to animal models. In the present review, we thoroughly examine and provide the state of the art of all these approaches.

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“…Notably, pathogenic defects in GDAP1 do not seem to impair peroxisomal fission [198], suggesting peroxisomal impairment is not relevant to the disease phenotype. Further supporting the important role for GDAP1 in neurons, GDAP1 knockout models in mice [196,200,207], fish [208], and Drosophila [209] also recapitulate neurological dysfunction. Importantly, mouse knockout models show axonal neuropathy as well as demyelination, and also exhibit larger mitochondria with anomalous axonal distribution [196,200].…”

Section: Ganglioside Induced Differentiation Associated Protein 1 (Gdap1)mentioning

confidence: 67%

Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

Sharma

Pfeffer

Shutt

2021

Biology

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Mitochondria are dynamic organelles capable of fusing, dividing, and moving about the cell. These properties are especially important in neurons, which in addition to high energy demand, have unique morphological properties with long axons. Notably, mitochondrial dysfunction causes a variety of neurological disorders including peripheral neuropathy, which is linked to impaired mitochondrial dynamics. Nonetheless, exactly why peripheral neurons are especially sensitive to impaired mitochondrial dynamics remains somewhat enigmatic. Although the prevailing view is that longer peripheral nerves are more sensitive to the loss of mitochondrial motility, this explanation is insufficient. Here, we review pathogenic variants in proteins mediating mitochondrial fusion, fission and transport that cause peripheral neuropathy. In addition to highlighting other dynamic processes that are impacted in peripheral neuropathies, we focus on impaired mitochondrial quality control as a potential unifying theme for why mitochondrial dysfunction and impairments in mitochondrial dynamics in particular cause peripheral neuropathy.

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A zebrafish model to study small-fiber neuropathy reveals a potential role for GDAP1

Cited by 14 publications

References 50 publications

An improved method for precise genome editing in zebrafish using CRISPR-Cas9 technique

An improved method for precise genome editing in zebrafish using CRISPR-Cas9 technique

Dominant Optic Atrophy (DOA): Modeling the Kaleidoscopic Roles of OPA1 in Mitochondrial Homeostasis

Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

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