PUBLICATION
Novel pre-clinical model for CDKL5 Deficiency Disorder
- Authors
- Serrano, R.J., Lee, C., Douek, A.M., Kaslin, J., Bryson-Richardson, R.J., Sztal, T.E.
- ID
- ZDB-PUB-211217-11
- Date
- 2021
- Source
- Disease models & mechanisms 15(3): (Journal)
- Registered Authors
- Bryson-Richardson, Robert, Douek, Alon M., Kaslin, Jan, Serrano, Rita, Sztal, Tamar Esther
- Keywords
- CDKL5 Deficiency Disorder, Locomotion, Microcephaly, Motor neurons, Seizure, Zebrafish
- MeSH Terms
-
- Animals
- Epileptic Syndromes
- Humans
- Neurodegenerative Diseases*
- Protein Serine-Threonine Kinases/genetics
- Quality of Life
- Spasms, Infantile
- Zebrafish*/genetics
- PubMed
- 34913468 Full text @ Dis. Model. Mech.
Citation
Serrano, R.J., Lee, C., Douek, A.M., Kaslin, J., Bryson-Richardson, R.J., Sztal, T.E. (2021) Novel pre-clinical model for CDKL5 Deficiency Disorder. Disease models & mechanisms. 15(3):.
Abstract
Cyclin-Dependent Kinase-Like-5 (CDKL5) Deficiency Disorder (CDD) is a severe X-linked neurodegenerative disease characterized by early-onset epileptic seizures, low muscle tone, progressive intellectual disability, and severe motor function. CDD affects approximately 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 pre-clinical 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 to investigate CDD disease pathophysiology and allow high-throughput screening for effective therapies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping