Abstract
The hypothalamic–pituitary–thyroid (HPT) axis regulates many critical features in vertebrates. Utilizing TALENs and CRISPR/Cas9 techniques, thyroid-stimulating hormone subunit beta a (tshba), thyroglobulin (tg), and solute carrier family 16 member 2 (slc16a2) mutant zebrafish lines were generated. Among the three mutants, the earliest time point for the significantly altered T3 contents was observed in tshba mutants, which resulted in the most severe defects, including typical defects such as the retardation of inflated anterior swimming bladder (aSB), proper formation of fin ray and posterior squamation (SP), the larval-to-juvenile transition (LTJT) process, juvenile growth retardation, and mating failure. In tg mutants, which are actually compensated with an alternative splicing form, growth retardation was observed in the juvenile stage without LTJT and reproductive defects. The evident goiter phenotype was only observed in tg- and slc16a2 mutants, but not in tshba mutants. Other than goiters being observed, no other significant developmental defects were found in the slc16a2 mutants. Regarding the reproductive defects observed in tshba mutants, the defective formation of the secondary sex characteristics (SSCs) was observed, while no obvious alterations during gonad development were found. Based on our analyses, zebrafish at the 6–12 mm standard length or 16–35 days post-fertilization (dpf) should be considered to be in their LTJT phase. Using a series of zebrafish dyshormonogenesis models, this study demonstrated that the TSH function is critical for the proper promotion of zebrafish LTJT and SSC formation. In addition, the elevation of TSH levels appears to be essential for goiter appearance in zebrafish.
Highlights
The thyroid hormone (TH) controls different processes in vertebrates, including metamorphosis, oxidative metabolism, and annual change of the photoperiod [1,2,3,4]
TSHβ was encoded by the tshba gene located at chromosome 6
The results showed that the sequence of the tshba mutant gene carried a 5-nucleotide deletion and a singlenucleotide substitution (G→C) on the tshba exon 3 (Figure 1C)
Summary
The thyroid hormone (TH) controls different processes in vertebrates, including metamorphosis, oxidative metabolism, and annual change of the photoperiod [1,2,3,4]. TSH, a heterodimer protein of two glycoprotein hormone subunits α and β, both of which are secreted from the anterior lobe of the pituitary gland, is a major signal that plays a positive regulatory role in thyroid homeostasis. Thyroglobulin (TG) is a large dimeric protein that is required for TH synthesis, storage, and secretion processes. After TH synthesis in the thyroid gland, solute carrier family 16 member 2 (SLC16A2) ( named monocarboxylate transporter 8) is a specific TH transporter in certain tissues that allows the cellular entry of THs to access their nuclear receptors for downstream TH signaling activation
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