論文 - 詳細
| RRC ID | 75003 |
|---|---|
| 著者 | Serrano RJ, Lee C, Douek AM, Kaslin J, Bryson-Richardson RJ, Sztal TE. |
| タイトル | Novel preclinical model for CDKL5 deficiency disorder. |
| ジャーナル | Dis Model Mech |
| Abstract |
Cyclin-dependent kinase-like-5 (CDKL5) deficiency disorder (CDD) is a severe X-linked neurodegenerative disease characterised by early-onset epileptic seizures, low muscle tone, progressive intellectual disability and severe motor function. CDD affects ∼1 in 60,000 live births, with many patients experiencing a reduced quality of life due to the severity of their neurological symptoms and functional impairment. There are no effective therapies for CDD, with current treatments focusing on improving symptoms rather than addressing the underlying causes of the disorder. Zebrafish offer many unique advantages for high-throughput preclinical evaluation of potential therapies for neurological diseases, including CDD. In particular, the large number of offspring produced, together with the possibilities for in vivo imaging and genetic manipulation, allows for the detailed assessment of disease pathogenesis and therapeutic discovery. We have characterised a loss-of-function zebrafish model for CDD, containing a nonsense mutation in cdkl5. cdkl5 mutant zebrafish display defects in neuronal patterning, seizures, microcephaly, and reduced muscle function caused by impaired muscle innervation. This study provides a powerful vertebrate model for investigating CDD disease pathophysiology and allowing high-throughput screening for effective therapies. This article has an associated First Person interview with the first author of the paper. |
| 巻・号 | 15(3) |
| 公開日 | 2022-3-1 |
| DOI | 10.1242/dmm.049094 |
| PII | 273746 |
| PMID | 34913468 |
| PMC | PMC8922025 |
| MeSH | Animals Epileptic Syndromes Humans Neurodegenerative Diseases* Protein Serine-Threonine Kinases / genetics Quality of Life Spasms, Infantile Zebrafish* / genetics |
| IF | 4.651 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 18 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | Tg(CM-isl1:GFP)rw0 |