Open AccessThyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish)
Author(s) -
Ciana Deveau,
Xiaodong Jiao,
Sachihiro C. Suzuki,
Asha Krishnakumar,
Takeshi Yoshimatsu,
J. Fielding Hejtmancik,
Ralph Nelson
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1008869
Subject(s) - biology , opsin , zebrafish , mutant , frameshift mutation , danio , microbiology and biotechnology , genetics , mutation , gene , biochemistry , retinal , rhodopsin
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.