Dépôt numérique

Generating a CRISPR/Cas9 zebrafish model to unravel SMA pathogenesis and for drug discovery

Préville, Marilou; Zaouter, Charlotte et Patten, Shunmoogum A. . Generating a CRISPR/Cas9 zebrafish model to unravel SMA pathogenesis and for drug discovery In: 11e European Zebrafish Meeting, 26-27 October 2020, virtuel.

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Spinal Muscular Atrophy (SMA) is a rare autosomal recessive neurodegenerative disease. It is the leading genetic cause of infant mortality for which there is currently no effective cure. SMA is characterized by a degeneration of lower alpha motoneurons of the spinal cord caused by the deletion of SMN1 gene on chromosome 5q13 leading to muscle weakness and atrophy. Although SMN is ubiquitously expressed, the mechanism underlying the degeneration of specifically the motoneurons remains poorly understood. Morpholino oligonucleotides based knockdown are commonly used in zebrafish to study SMA. However, the specificity of this technique is still controversial. Thus, we aim to generate a more reliable and stable model to study SMA. Using the CRISPR/Cas9 system, we targeted the zebrafish smn gene to create a knockout (KO) model. We successful identified a zebrafish smn KO mutant. These fish showed a significant reduced locomotion compared to controls. SMN protein levels were also significantly reduced in our smn zebrafish mutants. We are currently characterizing further our CRISPR/Cas9 model. Moreover, this model will be used for high throughput drug screening. In the long-term, our study may help find new avenues for therapeutic strategies in SMA.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique P069
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 14 juill. 2021 15:42
Dernière modification: 14 juill. 2021 15:42
URI: https://espace.inrs.ca/id/eprint/11858

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