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Fig. 10

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ZDB-IMAGE-160404-17
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Figures for Marelli et al., 2016
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Fig. 10

Rescue experiment using human wild-type and mutant TRs. Panels A-D) Embryos were coinjected with 0.6pmol/embryo of thraa splMO +200 pg/embryo of hTRα1_WT or 5 mutant hTRα (D211G (van Guchta et al., 2014), A263V (Moran et al., 2014), A382PfsX7 (Moran et al., 2013), E403X (Bochukova et al., 2012) and F397fs406X (van Mullem et al., 2012)) mRNAs and compared with the thraa_MOs. Panel A: embryos with “rescued phenotype” (normal development or mild defects). Panel B: embryos with “non-rescued phenotype” (moderate defects such as short body length and hypopigmentation, accompanied by cardiac (arrows) and brain edema (asterisks)). Panel C: qRT-PCR of deiodinase expression. The recovery of normal TH metabolism in embryos with rescued phenotype was confirmed by the reduced expression of dio2 and the increased expression of both dio3a and dio3b. **p < 0.01; ***p < 0.001 vs untreated thraa_MOs. Panel D: frequency of injected embryos belonging the two major classes. For each injection, the embryos were subdivided into two pools of 100 embryos each, and treated with DMSO (basal condition) or 15 µM T3 in the harvesting water. Panels E-G) Embryos were coinjected with 0.8pmol/embryo of thrb splMO +200 pg/embryo of hTRβ1_WT or hTRβ2_WT or 2 hTRβ mutant (R243Q (Onigata et al., 1995), PV (Parrilla et al., 1991)) mRNAs and compared with the thrb_MOs. Panel E: embryos with “rescued phenotype” (normal development or mild defects). Panel B: embryos with “non-rescued phenotype” (moderate defects such as curved tail, notochord alterations (asterisks) and eye hypopigmentation (arrows)). Panel G: qRT-PCR of tg and tshba expression. The recovery of normal thyroid function in embryos with reversed phenotype was confirmed by the reduced expression of tg and tshba. ***p < 0.001 vs untreated thrb_MOs. Panel H: frequency of injected embryos (treated with DMSO or 15 µM T3 in the harvesting water) belonging the two major classes.

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Reprinted from Molecular and Cellular Endocrinology, 424, Marelli, F., Carra, S., Agostini, M., Cotelli, F., Peeters, R., Chatterjee, K., Persani, L., Patterns of thyroid hormone receptor expression in zebrafish and generation of a novel model of resistance to thyroid hormone action, 102-17, Copyright (2016) with permission from Elsevier. Full text @ Mol. Cell. Endocrinol.