Thrb-flox Mouse

Thrb, short for thyroid hormone receptor beta, is a nuclear receptor encoded by the THRB gene. It plays a crucial role in mediating the action of thyroid hormone. Thyroid hormone action, mainly regulated by Thrb and Thra (thyroid hormone receptor alpha), impacts various biological processes including development, metabolism, and cell differentiation. 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 [3,4].

Mechanistic insights into Thrb's functions have been obtained from mouse models. For instance, introducing human THRB mutations into mice or deleting the mouse Thrb gene have revealed its contributions to processes like colour vision, cochlear and cerebellum development, and normal functioning of the adult liver and heart [4]. In a study on hPSC-derived hepatocytes, the addition of thyroid hormone T3 increased Thrb binding to the CYP3A4 proximal enhancer, restoring the super-enhancer status and gene expression of NFIC, and reducing the expression of AFP, thus facilitating their differentiation into more mature hepatocytes [1]. In another study, a fetal THRB genotype was found to influence the levels of TH regulators in the placenta [2].

In conclusion, Thrb is essential for mediating thyroid hormone action and is involved in multiple biological processes. Mouse models with Thrb mutations or deletions have significantly contributed to understanding its role in diseases such as RTHβ, as well as in other biological contexts like liver cell maturation and placental function.