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
  • Neurodegenerative Diseases*
  • Quality of Life
  • Protein Serine-Threonine Kinases/genetics
  • Spasms, Infantile
  • Epileptic Syndromes
  • Humans
  • Zebrafish*/genetics
  • Animals
(all 8)
PubMed
34913468 Full text @ Dis. Model. Mech.
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
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
jf5TgTransgenic Insertion
    knu3TgTransgenic Insertion
      rw0TgTransgenic Insertion
        sa21938
          Point Mutation
          1 - 4 of 4
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          Human Disease / Model
          Human Disease Fish Conditions Evidence
          epilepsyTAS
          microcephalyTAS
          1 - 2 of 2
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          Sequence Targeting Reagents
          Target Reagent Reagent Type
          cdkl5MO1-cdkl5MRPHLNO
          1 - 1 of 1
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          Fish
          Antibodies
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          GCaMPEFGGCaMP
          GFPEFGGFP
          1 - 3 of 3
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          Mapping
          No data available