| RRC ID |
64760
|
| 著者 |
Deveau C, Jiao X, Suzuki SC, Krishnakumar A, Yoshimatsu T, Hejtmancik JF, Nelson RF.
|
| タイトル |
Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish).
|
| ジャーナル |
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.
|
| 巻・号 |
16(6)
|
| ページ |
e1008869
|
| 公開日 |
2020-6-1
|
| DOI |
10.1371/journal.pgen.1008869
|
| PII |
PGENETICS-D-19-01687
|
| 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
|
| リソース情報 |
| ゼブラフィッシュ |
Tg(zfSWS2-3.5A:EGFP) kj11 |
