PLoS Genetics (Jun 2020)

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

  • Ciana Deveau,
  • Xiaodong Jiao,
  • Sachihiro C Suzuki,
  • Asha Krishnakumar,
  • Takeshi Yoshimatsu,
  • J Fielding Hejtmancik,
  • Ralph F Nelson

DOI
https://doi.org/10.1371/journal.pgen.1008869
Journal volume & issue
Vol. 16, no. 6
p. e1008869

Abstract

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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.