| First Author | Markossian S | Year | 2018 |
| Journal | Thyroid | Volume | 28 |
| Issue | 1 | Pages | 139-150 |
| PubMed ID | 29205102 | Mgi Jnum | J:268664 |
| Mgi Id | MGI:6273137 | Doi | 10.1089/thy.2017.0389 |
| Citation | Markossian S, et al. (2018) CRISPR/Cas9 Editing of the Mouse Thra Gene Produces Models with Variable Resistance to Thyroid Hormone. Thyroid 28(1):139-150 |
| abstractText | BACKGROUND: Resistance to thyroid hormone due to THRA mutations (RTHalpha) is a recently discovered genetic disease, displaying important variability in its clinical presentation. The mutations alter the function of TRalpha1, 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 RTHalpha, 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. |
