Thrb-KO Mouse

Thrb, short for thyroid hormone receptor beta, is a key gene encoding thyroid hormone receptors that mediate thyroid hormone action. Thyroid hormones play a crucial role in numerous biological processes such as metabolism, growth, and development. Mutations in Thrb are associated with resistance to thyroid hormone β (RTHβ), a disorder characterized by elevated thyroid hormone levels, normal or elevated TSH, and goitre [2,3].

Introducing human Thrb mutations into mice or deleting the mouse Thrb gene has provided insights into its functions. For instance, Thrb knockout mitigated the responsiveness of osteoblasts to short-and long-term thyroid hormone treatment in vitro, suggesting its importance in mediating thyroid hormone actions in bone [4]. In addition, in a 3D differentiation system for human PSCs into hepatocytes, reduced enrichment of Thrb motifs in accessible chromatin was observed without a reduction in its transcription, and adding thyroid hormone T3 enhanced Thrb binding to the CYP3A4 proximal enhancer, promoting hPSC-hepatocyte maturation [1].

In conclusion, Thrb is essential for normal thyroid hormone-mediated physiological processes. Mouse models with Thrb mutations or deletions have been instrumental in revealing its role in diseases like RTHβ, and in biological processes such as bone remodelling and hepatocyte maturation. Understanding Thrb functions helps in elucidating the pathophysiology of related diseases and potentially developing targeted therapies.

References:

1. Ma, Haiting, de Zwaan, Esmée, Guo, Yang Eric, Young, Richard A, Jaenisch, Rudolf. 2022. The nuclear receptor THRB facilitates differentiation of human PSCs into more mature hepatocytes. In Cell stem cell, 29, 795-809.e11. doi:10.1016/j.stem.2022.03.015. https://pubmed.ncbi.nlm.nih.gov/35452598/

2. Pappa, Theodora, Refetoff, Samuel. 2021. Resistance to Thyroid Hormone Beta: A Focused Review. In Frontiers in endocrinology, 12, 656551. doi:10.3389/fendo.2021.656551. https://pubmed.ncbi.nlm.nih.gov/33868182/

3. Ortiga-Carvalho, Tânia M, Sidhaye, Aniket R, Wondisford, Fredric E. 2014. Thyroid hormone receptors and resistance to thyroid hormone disorders. In Nature reviews. Endocrinology, 10, 582-91. doi:10.1038/nrendo.2014.143. https://pubmed.ncbi.nlm.nih.gov/25135573/

4. Lademann, Franziska, Tsourdi, Elena, Hofbauer, Lorenz C, Rauner, Martina. 2023. Thyroid hormone receptor Thra and Thrb knockout differentially affects osteoblast biology and thyroid hormone responsiveness in vitro. In Journal of cellular biochemistry, 124, 1948-1960. doi:10.1002/jcb.30500. https://pubmed.ncbi.nlm.nih.gov/37992217/