期刊
THYROID
卷 28, 期 1, 页码 139-150出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/thy.2017.0389
关键词
nuclear receptor; mouse model; CRISPR; Cas9
资金
- Agence Nationale de Recherche (Thyromut2 program) [ANR-15-CE14-0011-01]
- Fondation ARC pour la Recherche sur le Cancer [PGA1201402000834]
- Agence Nationale de la Recherche (ANR) [ANR-15-CE14-0011] Funding Source: Agence Nationale de la Recherche (ANR)
Background:Resistance to thyroid hormone due to THRA mutations (RTH) is a recently discovered genetic disease, displaying important variability in its clinical presentation. The mutations alter the function of TR1, 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 RTH, 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.
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