RRC ID 64760
Author Deveau C, Jiao X, Suzuki SC, Krishnakumar A, Yoshimatsu T, Hejtmancik JF, Nelson RF.
Title Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish).
Journal PLoS Genet
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. Our results confirm a critical role for trβ2 in long-wavelength cone development.
Volume 16(6)
Pages e1008869
Published 2020-6-1
DOI 10.1371/journal.pgen.1008869
PMID 32569302
PMC PMC7332105
MeSH 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
IF 5.175
Zebrafish Tg(zfSWS2-3.5A:EGFP) kj11