Steroid receptor coactivator (SRC) -1 and transcriptional intermediary factor (TIF) -2 are homologous nuclear receptor coactivators. We have investigated their possible redundancy as thyroid hormone (TH) coactivators by measuring thyroid function in compound SRC-1 and TIF-2 knock out (KO) mice. Whereas SRC-1 KO (SRC-1-/-) mice are resistant to TH and SRC-1+/- are not, we now demonstrate that TIF-2 KO (TIF-2-/-) mice have normal thyroid function. Yet double heterozygous, SRC-1+/-/TIF-2+/- mice manifested resistance to TH of a similar degree as that in mice completely deficient in SRC-1. KO of both SRC-1 and TIF-2 resulted in marked increases of serum TH and thyrotropin concentrations. This work demonstrates gene dosage effect in nuclear coactivators manifesting as haploinsufficiency and functional redundancy of SRC-1 and TIF-2.
ASJC Scopus subject areas