ZFIN ID: ZDB-PUB-200623-5
Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish)
Deveau, C., Jiao, X., Suzuki, S.C., Krishnakumar, A., Yoshimatsu, T., Hejtmancik, J.F., Nelson, R.F.
Date: 2020
Source: PLoS Genetics   16: e1008869 (Journal)
Registered Authors: Hejtmancik, J. Fielding, Nelson, Ralph
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation/genetics
  • Color Vision/genetics*
  • Cone Opsins/genetics
  • Cone Opsins/metabolism
  • Frameshift Mutation
  • Gene Expression Regulation, Developmental*
  • Genes, erbA/genetics*
  • INDEL Mutation
  • Larva
  • Models, Animal
  • Photoreceptor Cells, Invertebrate/pathology
  • Retina/cytology
  • Retina/growth & development*
  • Retina/pathology
  • Sequence Deletion
  • Thyroid Hormone Receptors beta/genetics*
  • Trans-Activators/genetics
  • Trans-Activators/metabolism
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 32569302 Full text @ PLoS Genet.
We investigate mutations in trβ2, a splice variant of thrb, identifying changes in function, structure, and behavior in larval and adult zebrafish retinas. Two N-terminus CRISPR mutants were identified. The first is a 6BP+1 insertion deletion frameshift resulting in a truncated protein. The second is a 3BP in frame deletion with intact binding domains. ERG recordings of isolated cone signals showed that the 6BP+1 mutants did not respond to red wavelengths of light while the 3BP mutants did respond. 6BP+1 mutants lacked optomotor and optokinetic responses to red/black and green/black contrasts. Both larval and adult 6BP+1 mutants exhibit a loss of red-cone contribution to the ERG and an increase in UV-cone contribution. Transgenic reporters show loss of cone trβ2 activation in the 6BP+1 mutant but increase in the density of cones with active blue, green, and UV opsin genes. Antibody reactivity for red-cone LWS1 and LWS2 opsin was absent in the 6BP+1 mutant, as was reactivity for arrestin3a. Our results confirm a critical role for trβ2 in long-wavelength cone development.