PUBLICATION

Evaluation of two gene ablation methods for the analysis of pregnenolone function in zebrafish embryonic development

Authors
Kolas, V., Mathieu, G., Wu, Y.T., Chung, B.C.
ID
ZDB-PUB-221105-4
Date
2022
Source
Biochemical and Biophysical Research Communications   636: 84-88 (Journal)
Registered Authors
Chung, Bon-chu
Keywords
CRISPR, Microtubule, Morpholino, P5, clip1, cyp11a1
MeSH Terms
  • Animals
  • Cholesterol Side-Chain Cleavage Enzyme*/genetics
  • Cholesterol Side-Chain Cleavage Enzyme*/metabolism
  • Embryonic Development/genetics
  • Morpholinos/metabolism
  • Pregnenolone/metabolism
  • Zebrafish*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
36332486 Full text @ Biochem. Biophys. Res. Commun.
Abstract
Pregnenolone (P5) is a steroid that functions in the brain and in zebrafish embryogenesis. It is synthesized from cholesterol via the enzymatic activity of P450scc, encoded by CYP11A1. P5 exerts its function by activating CLIP1, which in turn promotes microtubule assembly necessary for many biological processes including embryogenesis. To examine the functional relatedness of CYP11A1 and CLIP1, we ablated the embryonic expression of both genes in zebrafish, i.e. cyp11a1 and clip1a. Two cyp11a1 knockout fish lines were generated. Both homozygous cyp11a1 knockout lines appeared normal. But the development of fish embryos was delayed and embryonic cell migration was reduced when cyp11a1 function was depleted of by morpholinos. This discrepancy in phenotypes by two different gene depletion methods was also observed for clip1a. While clip1a morphants are defective in embryogenesis, clip1a knockout fish appeared normal. The phenotypes depend on the methods that create gene depletion. While knockout fish lines do not have expected phenotypic defects, clip1a and cyp11a1 morpholinos both reduce embryonic cell migration. We have evaluated the usefulness of both methods of gene ablation, and conclude that CYP11A1 and CLIP1 function in the same pathway to promote embryogenesis.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping