Cargando…

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

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 i...

Descripción completa

Detalles Bibliográficos
Autores principales: Deveau, Ciana, Jiao, Xiaodong, Suzuki, Sachihiro C., Krishnakumar, Asha, Yoshimatsu, Takeshi, Hejtmancik, J Fielding, Nelson, Ralph F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332105/
https://www.ncbi.nlm.nih.gov/pubmed/32569302
http://dx.doi.org/10.1371/journal.pgen.1008869
_version_ 1783553463670538240
author Deveau, Ciana
Jiao, Xiaodong
Suzuki, Sachihiro C.
Krishnakumar, Asha
Yoshimatsu, Takeshi
Hejtmancik, J Fielding
Nelson, Ralph F.
author_facet Deveau, Ciana
Jiao, Xiaodong
Suzuki, Sachihiro C.
Krishnakumar, Asha
Yoshimatsu, Takeshi
Hejtmancik, J Fielding
Nelson, Ralph F.
author_sort Deveau, Ciana
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7332105
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-73321052020-07-15 Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish) Deveau, Ciana Jiao, Xiaodong Suzuki, Sachihiro C. Krishnakumar, Asha Yoshimatsu, Takeshi Hejtmancik, J Fielding Nelson, Ralph F. PLoS Genet Research Article 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. Public Library of Science 2020-06-22 /pmc/articles/PMC7332105/ /pubmed/32569302 http://dx.doi.org/10.1371/journal.pgen.1008869 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Deveau, Ciana
Jiao, Xiaodong
Suzuki, Sachihiro C.
Krishnakumar, Asha
Yoshimatsu, Takeshi
Hejtmancik, J Fielding
Nelson, Ralph F.
Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish)
title Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish)
title_full Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish)
title_fullStr Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish)
title_full_unstemmed Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish)
title_short Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish)
title_sort thyroid hormone receptor beta mutations alter photoreceptor development and function in danio rerio (zebrafish)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332105/
https://www.ncbi.nlm.nih.gov/pubmed/32569302
http://dx.doi.org/10.1371/journal.pgen.1008869
work_keys_str_mv AT deveauciana thyroidhormonereceptorbetamutationsalterphotoreceptordevelopmentandfunctionindanioreriozebrafish
AT jiaoxiaodong thyroidhormonereceptorbetamutationsalterphotoreceptordevelopmentandfunctionindanioreriozebrafish
AT suzukisachihiroc thyroidhormonereceptorbetamutationsalterphotoreceptordevelopmentandfunctionindanioreriozebrafish
AT krishnakumarasha thyroidhormonereceptorbetamutationsalterphotoreceptordevelopmentandfunctionindanioreriozebrafish
AT yoshimatsutakeshi thyroidhormonereceptorbetamutationsalterphotoreceptordevelopmentandfunctionindanioreriozebrafish
AT hejtmancikjfielding thyroidhormonereceptorbetamutationsalterphotoreceptordevelopmentandfunctionindanioreriozebrafish
AT nelsonralphf thyroidhormonereceptorbetamutationsalterphotoreceptordevelopmentandfunctionindanioreriozebrafish