Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish)

PLoS Genet. 2020 Jun 22;16(6):e1008869. doi: 10.1371/journal.pgen.1008869. eCollection 2020 Jun.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

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


  • Cone Opsins
  • Opn1lw1 protein, zebrafish
  • Thyroid Hormone Receptors beta
  • Trans-Activators
  • Zebrafish Proteins
  • cxxc1b protein, zebrafish

Associated data

  • Dryad/10.5061/dryad.msbcc2fvr

Grants and funding

The research was supported by the Intramural Program of the National Institute of Neurological Disorders and Stroke (R.N) and the Intramural Program of the National Eye Institute, National Institutes of Health (F.H), and by National Institutes of Health Grant EY14356 (to Rachel O. L. Wong, S.S and T.Y.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.