PUBLICATION
Patterns of thyroid hormone receptor expression in zebrafish and generation of a novel model of resistance to thyroid hormone action
- Authors
- Marelli, F., Carra, S., Agostini, M., Cotelli, F., Peeters, R., Chatterjee, K., Persani, L.
- ID
- ZDB-PUB-160124-1
- Date
- 2016
- Source
- Molecular and Cellular Endocrinology 424: 102-17 (Journal)
- Registered Authors
- Cotelli, Franco
- Keywords
- Resistance to Thyroid Hormone, THRA, THRB, Thyroid hormone action, Thyroid hormone receptors, Zebrafish
- MeSH Terms
-
- Animals
- Disease Models, Animal*
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental
- Humans
- Mutation
- Thyroid Hormone Receptors alpha/genetics*
- Thyroid Hormone Receptors alpha/metabolism
- Thyroid Hormone Receptors beta/genetics*
- Thyroid Hormone Receptors beta/metabolism
- Thyroid Hormone Resistance Syndrome/genetics*
- Thyroid Hormones/metabolism*
- Tissue Distribution
- Zebrafish/genetics
- Zebrafish/growth & development*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 26802880 Full text @ Mol. Cell. Endocrinol.
Citation
Marelli, F., Carra, S., Agostini, M., Cotelli, F., Peeters, R., Chatterjee, K., Persani, L. (2016) Patterns of thyroid hormone receptor expression in zebrafish and generation of a novel model of resistance to thyroid hormone action. Molecular and Cellular Endocrinology. 424:102-17.
Abstract
Resistance to thyroid hormone can be due to heterozygous, dominant negative (DN) THRA (RTHα) or THRB (RTHβ) mutations, but the underlying mechanisms are incompletely understood. Here, we delineate the spatiotemporal expression of TH receptors (TRs) in zebrafish and generated morphants expressing equivalent amounts of wild-type and DN TRαs (thraa_MOs) and TRβs (thrb_MOs) in vivo. Both morphants show severe developmental abnormalities. The phenotype of thraa_MOs includes brain and cardiac defects, but normal thyroid volume and tshba expression. A combined modification of dio2 and dio3 expression can explain the high T3/T4 ratio seen in thraa_MOs, as in RTHα. Thrb_MOs show abnormal eyes and otoliths, with a typical RTHβ pattern of thyroid axis. The coexpression of wild-type, but not mutant, human TRs can rescue the phenotype in both morphants. High T3 doses can partially revert the dominant negative action of mutant TRs in morphant fish. Therefore, our morphants recapitulate the RTHα and RTHβ key manifestations representing new models in which the functional consequences of human TR mutations can be rapidly and faithfully evaluated.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping