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Roy E. Weiss, Martine Gehin, Jianming Xu, Peter M. Sadow, Bert W. O’Malley, Pierre Chambon, Samuel Refetoff, Thyroid Function in Mice with Compound Heterozygous and Homozygous Disruptions of SRC-1 and TIF-2 Coactivators: Evidence for Haploinsufficiency, Endocrinology, Volume 143, Issue 4, 1 April 2002, Pages 1554–1557, https://doi.org/10.1210/endo.143.4.8828
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Abstract
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.