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.
Citation
Rozenblat, R., Tovin, A., Zada, D., Lebenthal-Loinger, I., Lerer-Goldshtein, T., Appelbaum, L. (2022) Genetic and Neurological Deficiencies in the Visual System of mct8 Mutant Zebrafish. International Journal of Molecular Sciences. 23(5):.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping