PUBLICATION

Genetic and Neurological Deficiencies in the Visual System of mct8 Mutant Zebrafish

Authors
Rozenblat, R., Tovin, A., Zada, D., Lebenthal-Loinger, I., Lerer-Goldshtein, T., Appelbaum, L.
ID
ZDB-PUB-220311-20
Date
2022
Source
International Journal of Molecular Sciences   23(5): (Journal)
Registered Authors
Appelbaum, Lior, Rozenblat, Rotem, Zada, David
Keywords
OKR, monocarboxylate transporter 8, opsin, pretectum, thyroid hormones, zebrafish
MeSH Terms
  • Animals
  • Brain/metabolism
  • Humans
  • Hypothyroidism*/metabolism
  • Monocarboxylic Acid Transporters/genetics
  • Monocarboxylic Acid Transporters/metabolism
  • Symporters*/genetics
  • Symporters*/metabolism
  • Thyroid Hormones/genetics
  • Thyroid Hormones/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed
35269606 Full text @ Int. J. Mol. Sci.
Abstract
Thyroid hormones (THs; T3 and T4) enter cells using specific transporters and regulate development and metabolism. Mutation in the TH transporter monocarboxylate transporter 8 (MCT8, SLC16A2) is associated with brain hypothyroidism and neurological impairment. We established mct8 mutant (mct8-/-) zebrafish as a model for MCT8 deficiency, which causes endocrinological, neurological, and behavioral alterations. Here, we profiled the transcriptome of mct8-/- larvae. Among hundreds of differentially expressed genes, the expression of a cluster of vision-related genes was distinct. Specifically, the expression of the opsin 1 medium wave sensitive 2 (opn1mw2) decreased in two mct8 mutants: mct8-/- and mct8-25bp-/- larvae, and under pharmacological inhibition of TH production. Optokinetic reflex (OKR) assays showed a reduction in the number of conjugated eye movements, and live imaging of genetically encoded Ca2+ indicator revealed altered neuronal activity in the pretectum area of mct8-25bp-/- larvae. These results imply that MCT8 and THs regulate the development of the visual system and suggest a mechanism to the deficiencies observed in the visual system of MCT8-deficiency patients.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping