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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere1008869
JournalPLoS genetics
Volume16
Issue number6
DOIs
StatePublished - Jun 2020

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