PUBLICATION

Effects of serta and sertb knockout on aggression in zebrafish (Danio rerio)

Authors
Tea, M., Pan, Y.K., Lister, J.G.R., Perry, S.F., Gilmour, K.M.
ID
ZDB-PUB-240229-2
Date
2024
Source
Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology   210(5): 785-799 (Journal)
Registered Authors
Gilmour, Kathleen M, Perry, Steve F.
Keywords
5-HT, 5-HT receptor, Aggression, Mirror test, Monoamine oxidase, Tryptophan hydroxylase
MeSH Terms
  • Gene Knockout Techniques
  • Animals
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Female
  • Serotonin Plasma Membrane Transport Proteins*/genetics
  • Serotonin Plasma Membrane Transport Proteins*/metabolism
  • Serotonin/metabolism
  • Aggression*/physiology
  • Behavior, Animal/physiology
  • CRISPR-Cas Systems
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Male
  • Brain/metabolism
  • Animals, Genetically Modified
PubMed
38416162 Full text @ J. Comp. Physiol. A
Abstract
Zebrafish (Danio rerio) are unusual in having two paralogues of the serotonin re-uptake transporter (Sert), slc6a4a (serta) and slc6a4b (sertb), the transporter that serves in serotonin re-uptake from a synapse into the pre-synaptic cell or in serotonin uptake from the extracellular milieu into cells in the peripheral tissues. To address a knowledge gap concerning the specific roles of these paralogues, we used CRISPR/Cas9 technology to generate zebrafish knockout lines predicted to lack functional expression of Serta or Sertb. The consequences of loss-of-function of Serta or Sertb were assessed at the gene expression level, focusing on the serotonergic signalling pathway, and at the behaviour level, focusing on aggression. Whereas serta mRNA was expressed in all tissues examined, with high expression in the heart, gill and brain, only the brain displayed substantial sertb mRNA expression. In both serta-/- and sertb-/- fish, changes in transcript abundances of multiple components of the serotonin signalling pathway were detected, including proteins involved in serotonin synthesis (tph1a, tph1b, tph2, ddc), packaging (vmat2) and degradation (mao), and serotonin receptors (htr1aa, htr1ab). Using a mirror aggression test, serta-/- male but not female fish exhibited greater aggression than wildtype fish. However, both male and female sertb-/- fish displayed less aggression than their wildtype counterparts. These differences in behaviour between serta-/- and sertb-/- individuals hold promise for increasing our understanding of the neurophysiological basis of aggression in zebrafish.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping