THRB and hypothyroidism: In mouse lines meant to mimic hypothyroidism (TRα and TRβ KO), TRβ KO mice demonstrated no alterations in HCN expression level or HR, whereas the TRα KO had decreased HR and a reduction in both HCN2 and HCN4 expression levels, implying that the effects of T3 on HCN channel expression occur through activation of TRα (Gloss et al., 2001).