BACKGROUND: Resistance to thyroid hormone due to THRA mutations (RTHα) is a recently discovered genetic disease, displaying important variability in its clinical presentation. The mutations alter the function of TRα1, one of the two nuclear receptors for thyroid hormone. METHODS: The aim of this study was to understand the relationship between specific THRA mutations and phenotype. CRISPR/Cas9 genome editing was used to generate five new mouse models of RTHα, with frameshift or missense mutations. RESULTS: Like human patients, mutant mice displayed a hypothyroid-like phenotype, with altered development. Phenotype severity varied between the different mouse models, mainly depending on the ability of the mutant receptor to interact with transcription corepressor in the presence of thyroid hormone. CONCLUSION: The present mutant mice represent highly relevant models for the human genetic disease which will be useful for future investigations.
BACKGROUND: Resistance to thyroid hormone due to THRA mutations (RTHα) is a recently discovered genetic disease, displaying important variability in its clinical presentation. The mutations alter the function of TRα1, one of the two nuclear receptors for thyroid hormone. METHODS: The aim of this study was to understand the relationship between specific THRA mutations and phenotype. CRISPR/Cas9 genome editing was used to generate five new mouse models of RTHα, with frameshift or missense mutations. RESULTS: Like humanpatients, mutant mice displayed a hypothyroid-like phenotype, with altered development. Phenotype severity varied between the different mouse models, mainly depending on the ability of the mutant receptor to interact with transcription corepressor in the presence of thyroid hormone. CONCLUSION: The present mutant mice represent highly relevant models for the humangenetic disease which will be useful for future investigations.
Authors: Pamela D Noyes; Katie Paul Friedman; Patience Browne; Jonathan T Haselman; Mary E Gilbert; Michael W Hornung; Stan Barone; Kevin M Crofton; Susan C Laws; Tammy E Stoker; Steven O Simmons; Joseph E Tietge; Sigmund J Degitz Journal: Environ Health Perspect Date: 2019-09-05 Impact factor: 9.031
Authors: Beatriz Romartinez-Alonso; Maura Agostini; Heulyn Jones; Jayde McLellan; D Eilidh Sood; Nicholas Tomkinson; Federica Marelli; Ilaria Gentile; W Edward Visser; Erik Schoenmakers; Louise Fairall; Martin Privalsky; Carla Moran; Luca Persani; Krishna Chatterjee; John W R Schwabe Journal: Mol Cell Biol Date: 2021-12-06 Impact factor: 4.272